A Cross-Sectional Study of Health-Related Quality of Life in Patients with Predominantly Antibody Deficiency 

A Cross-Sectional Study of Health-Related Quality of Life in Patients with Predominantly Antibody Deficiency | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Cross-Sectional Study of Health-Related Quality of Life in Patients with Predominantly Antibody Deficiency Ahmed Elmoursi, Baijun Zhou, Mei-Sing Ong, Joseph S. Hong, Andrew Pak, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4612913/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Aug, 2024 Read the published version in Journal of Clinical Immunology → Version 1 posted 7 You are reading this latest preprint version Abstract Health-related quality of life (HRQoL) measures individual well-being across physical, psychological, and social domains. Patients with predominantly antibody deficiency (PAD) are at risk for morbidity and mortality, however, the effect of these complications on HRQoL requires additional study. Patients with PAD were asked to voluntarily complete the Centers for Disease Control (CDC) HRQoL-14 Healthy Days Measure questionnaire. These results were compared to data from the CDC-initiated Behavioral Risk Factor Surveillance System (BRFSS), a cross-sectional questionnaire including questions from CDC-HRQOL-14. Statistical analyses included two-proportion Z-test, t-tests, and analysis of variance. 83 patients with PAD completed the survey. Patients were sub-stratified into mild (23.7%), moderate (35.5%), severe (40.8%), and secondary (8.4%) PAD. "Fair or poor" health status was reported in 52.6% of PAD patients. Mental health challenges ≥ 14 days/month occurred in 25% of patients. Physical health issues ≥ 14 days/month was reported in 44.7% of patients. Activity limitations were noted by 80.3% of patients. There were no statistically significant differences by PAD severity. Patients with autoinflammatory disease co-morbidities reported more mental health challenges compared to those without (78% vs. 54.3%, p = 0.02). Compared to the CDC-BRFSS data, significantly more patients with PAD reported "fair or poor" health status (53% vs 12.0%; p < 0.0001), mental health challenges (24.1% vs 14.7%; p = 0.02), and poor physical health (44.6% vs 8.0%; p < 0.0001). Patients with PAD had significantly reduced HRQoL compared to CDC-BRFSS respondents from a similar geographical region. Decreased HRQoL was prevalent across all PAD severity levels. Additional research is needed to improve HRQoL for patients with PAD. Predominantly antibody deficiency Health-related quality of life CDC HRQoL-14 Behavioral risk factor surveillance system Immunodeficiency Common variable immunodeficiency Hypogammaglobulinemia Immunoglobulin therapy Chronic disease management Mental health Physical health Patient-reported outcomes Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 INTRODUCTION Predominantly antibody deficiency (PAD) is the most frequently diagnosed inborn error of immunity (IEI) and the most common primary immunodeficiency disorder worldwide.( 1 – 5 ) Patients with PAD are susceptible to recurrent infections due to reduced antibody levels and/or inadequate vaccination responses.( 6 , 7 ) However, the impact of PAD extends beyond recurrent infections; affected individuals often face a spectrum of comorbidities, including autoimmune diseases and lymphoproliferative disorders, which can contribute to progressive end-organ damage and a diminished life expectancy.( 3 ) The concept of health-related quality of life (HRQoL) is becoming increasingly recognized as an important metric for evaluating patient well-being and for guiding therapeutic choices in both clinical and research settings.( 8 ) HRQoL captures a comprehensive, multifaceted evaluation of an individual's physical, psychological, emotional, and social functioning. This in turn reflects a wide-ranging and complex domain of interest among diverse stakeholders including healthcare providers, researchers, policymakers, and families.( 8 – 10 ) Increasing evidence positions HRQoL as an essential indicator for assessing treatment effectiveness and the overall health of those with chronic conditions. This approach extends beyond traditional clinical measures such as survival, adverse events, and death rates to offer a holistic view of the effects of disease and treatment on a patient's life from their own perspective.( 11 , 12 ) Studies have shown that HRQoL measurements, when tailored to specific conditions, provide a more precise evaluation of the impacts of medical interventions on patient lives when compared to general clinical assessments. ( 13 ) This approach facilitates the identification of various health determinants and guides the development of personalized treatment, management, and preventive strategies, aligning with healthcare’s ultimate goal of enhancing QoL while also prolonging lives. ( 14 ) The principal strategy for both prophylaxis and management of PAD is the administration of immunoglobulin G (IgG) replacement, either intravenously (IVIG) or subcutaneously (SCIG). This therapeutic approach has proven to be both effective and safe in reducing the incidence and severity of infections in PAD patients.( 15 ) Despite this, patients continue to face ongoing challenges, such as recurrent infections, autoimmune and lymphoproliferative complications, and the need for frequent acute care visits. These challenges are attributed to the chronic nature of PAD, treatment side effects, and the complexities of their care management. This limits patients’ social and physical activities ( 16 , 17 ), contributing to an increased risk of fatigue ( 18 ), depression ( 19 ), anxiety ( 20 ), cardiovascular diseases, cancer, sleep disorders, and mental health conditions ( 21 – 23 ), which may severely affect their psychological and physical health, and consequently, reduce their overall quality of life (QoL). Despite the progress in treatment modalities that have improved survival rates for individuals with PAD, the impact of PAD on HRQoL has not been thoroughly researched. Therefore, we sought to assess HRQoL in PAD by utilizing the Centers for Disease Control (CDC) Health-Related Quality of Life (HRQoL)-14 Healthy Days Measure questionnaire ( 24 ), and to compare the HRQoL of PAD patients with that of the general population, utilizing data from the CDC's Behavioral Risk Factor Surveillance System (BRFSS).( 25 , 26 ) METHODS This cross-sectional observational study was designed to assess the HRQoL in patients diagnosed with PAD. Adult PAD patients (age ≥ 18 years) were consented at Mass General Brigham (MGB). Participants voluntarily completed the Centers for Disease Control (CDC) HRQoL-14 Healthy Days Measure questionnaire ( 24 ) during routine visits or at intermittent time points. This was conducted under an Institutional Review Board (IRB) approved protocol (#2018P002713) between September 24, 2019, and February 12, 2024. The diagnoses of PAD were confirmed through manual chart review by a clinical immunologist, and met consensus definitions.( 6 , 27 , 28 ) A total of 83 patients with PAD were included. HRQoL-14 Healthy Days Measure is a self-report questionnaire designed to assess HRQoL among adult participants. It contains 14 items distributed across two primary dimensions: Mental Health (MH) (4 items), and Physical Health (PH) (10 items). Some items are assessed on a categorical scale and others require respondents to provide a continuous measure, such as reporting the number of unhealthy days they have experienced within the past 30 days. Taken together, these measures indicate a patient’s health status with a higher count suggesting a poorer health condition. Supplementary sections delve into specifics such as activity limitations and health symptoms such as pain, depression, anxiety, sleep disorders, and energy levels. It also inquires about respondents' recent health conditions and any limitations to their activities. The completion of the questionnaire typically requires no more than five minutes. The total and dimensional scores are interpreted directly, with no need for transformation to a percentage of a maximum possible score. For items with missing responses, the CDC provides guidelines on how to handle incomplete data based on the specific requirements of the analysis.( 24 ) The questionnaire was originally developed in English and is publicly available for use. Patients with PAD were subclassified as mild (Primary hypogammaglobulinemia, IgG subclass deficiency, and specific antibody deficiency [SAD]), moderate (uncomplicated common variable immunodeficiency [CVID]), and severe (complicated PAD defined as a presence of co-occurring autoinflammatory clinical features ( 28 )), as previously published.( 29 , 30 ) Patients with confounding variables at the time of immunodeficiency diagnosis (e.g., clonal lymphocyte population or ongoing immunosuppression without the potential for discontinuation) were considered to be secondary PAD. We compared the responses across the three severity levels among primary PAD patients, and further we compared responses from PAD patients with data from the CDC-initiated Behavioral Risk Factor Surveillance System (BRFSS), which included HRQOL-14 responses from a control comparator group of the general population in the Boston area, consisting of 801,582 respondents, in 2021.( 25 , 26 ) Data were collected on patient demographics including age, gender, race, and specific PAD diagnoses. Information regarding clinical characteristics and disease severity was gathered through patient medical records. Descriptive statistics were used to summarize the sample characteristics, with mean values described for continuous variables and frequencies and percentages for categorical variables. We used a two-proportion Z-test to compare the responses from PAD patients in our study with the CDC-BRFSS data. Chi-square tests and analyses of variance (ANOVA) were used to compare the responses across three severity levels among PAD patients. Statistical analyses were completed with SAS 9.4 (SAS Institute, Cary, NC) and Prism Version 7.01 (Reston, VA). A two-tailed p-value of < 0.05 was considered significant. RESULTS PAD patient demographics This cross-sectional observational study evaluated 83 adult patients diagnosed with PAD using the CDC HRQoL-14 Healthy Days Measure questionnaire. Among these patients, 91.6% (n = 76) had primary PAD and 8.4% (n = 7) had secondary PAD. The average age of participants was 54.8 years, with a standard deviation (SD) of 15.4 years. 71% were female and 97.6% were non-Hispanic White. The most common type of PAD was complicated Common Variable Immunodeficiency (CVID) (e.g. CVID with autoinflammatory features or a more severe immunophenotype), observed in 53% of patients (n = 44), followed by uncomplicated CVID, which constituted 24.1% (n = 20) of the cases. Primary hypogammaglobulinemia was present in 8.4% (n = 7) of participants, secondary hypogammaglobulinemia in 8.4% (n = 7), specific antibody deficiency accounted for in 3.6% (n = 3), and IgG subclass deficiency accounted for 2.4% (n = 2) of the PAD types within our study population (Table 1 ). Primary PAD patients were stratified by their disease severity; 23.7% (n = 18) had mild PAD, 35.5% (n = 27) had moderate PAD, and 40.8% (n = 31) had severe PAD. This sample was representative of our overall MGB cohort of patients with PAD in terms of age, race/ethnicity, and disease distribution (Table S1). Table 1 Patient demographics Predominantly antibody deficiency, n 83 Average age (years, [std]) 54.8 (15.4) Sex Male (% [n]) 28.9 ( 24 ) Female (% [n]) 71.1 (59) Race (% [n]) Non-Hispanic White 97.6 (81) Black/African American 0 (0) Asian 1.2 ( 1 ) American Indian/Alaska 0 (0) Native Hawaiian Other Pacific Islander 0 (0) Declined/Two or more/Other/Unknown 1.2 ( 1 ) Predominantly antibody deficiency type (% [n]) Complicated CVID 53.0 (44) Common variable immunodeficiency (CVID) 24.1 ( 20 ) Primary Hypogammaglobulinemia 8.4 ( 7 ) Secondary Hypogammaglobulinemia 8.4 ( 7 ) Specific antibody deficiency 3.6 ( 3 ) IgG subclass deficiency 2.4 ( 2 ) HRQoL in PAD patients We compared the HRQoL in adult patients with primary PAD, stratified by disease severity. Our analysis compared core and individual HRQoL-14 questions across mild, moderate, and severe PAD patient groups (Table 2 ). Core HRQoL questions evaluated patients' perceptions of their overall health and the extent to which they experienced periods of suboptimal mental or physical health lasting more than two weeks. Table 2 Comparison of HRQoL-14 responses among mild, moderate, and severe PAD patients. Mild PAD (n = 18) Moderate PAD (n = 27) Severe PAD (n = 31) P-value Core questions Fair or poor self-rated health status (% [n]) 66.7 ( 12 ) 40.7 ( 11 ) 54.8 ( 17 ) 0.22 Mental health not good for ≥ 14 days (% [n]) 16.7 ( 3 ) 33.3 ( 9 ) 22.6 ( 7 ) 0.41 Physical health not good for ≥ 14 days (% [n]) 38.9 ( 7 ) 44.4 ( 12 ) 48.4 ( 15 ) 0.81 Individual questions Activity limitation due to health problem a (% [n]) 88.9 ( 16 ) 92.0 ( 23 ) 71.0 ( 22 ) 0.11 Need for personal care assistance b (% [n]) 5.6 ( 1 ) 14.8 ( 4 ) 13.3 ( 4 ) 0.74 Need for assistance with routine needs c (% [n]) 50.0 ( 9 ) 51.9 ( 14 ) 36.7 ( 11 ) 0.47 Number of days during the past 30 days with poor physical health d (mean [std]) 13.4 (11.3) 13.1 (10.2) 13.6 (11.5) 0.98 Number of days during the past 30 days with poor mental health e (mean [std]) 5.5 (8.2) 10.6 (10.4) 8.0 (8.8) 0.19 Number of days during the past 30 days that poor physical or mental health affected usual activities f (mean [std]) 9.7 (10.4) 11.4 (9.9) 9.0 (9.2) 0.64 Number of months that activities limited by health problem (mean [std]) 32.0 (34.2) 111.5 (380.0) 52.2 (79.5) 0.48 Number of days during the past 30 days that pain impacted usual activities (e.g., self-care, work, or recreation (mean [std]) 11.3 (11.2) 9.4 (9.3) 9.0 (10.6) 0.74 Number of days during the past 30 days felt depressed g (mean [std]) 4.3 (8.2) 9.5 (9.3) 4.8 (7.9) 0.06 Number of days during the past 30 days felt anxious or tense h (mean [std]) 8.9 (10.9) 12.6 (10.8) 7.0 (8.0) 0.10 Number of days during the past 30 days lacked sufficient rest or sleep i (mean [std]) 14.9 (11.0) 15.2 (9.9) 11.4 (11.1) 0.34 Number of days during the past 30 days felt health and energetic j (mean [std]) 6.1 (8.9) 5.5 (7.4) 10.0 (11.0) 0.16 a Are you LIMITED in any way in any activities because of any impairment or health problem? b Because of any impairment or health problem, do you need the help of other persons with your PERSONAL CARE needs, such as eating, bathing, dressing, or getting around the house? c Because of any impairment or health problem, do you need the help of other persons in handling your ROUTINE needs, such as everyday household chores, doing necessary business, shopping, or getting around for other purposes? d Now thinking about your physical health, which includes physical illness and injury, for how many days during the past 30 days was your physical health not good? e Now thinking about your mental health, which includes stress, depression, and problems with emotions, for how many days during the past 30 days was your mental health not good? f During the past 30 days, for about how many days did poor health keep you from doing your usual activities, such as self-care, work, or recreation? g During the past 30 days, for about how many days have you felt SAD, BLUE, or DEPRESSED? h During the past 30 days, for about how many days have you felt WORRIED, TENSE, or ANXIOUS? i During the past 30 days, for about how many days have you felt you did NOT get ENOUGH REST or SLEEP? j During the past 30 days, for about how many days have you felt VERY HEALTHY AND FULL OF ENERGY? The assessment of fair or poor self-rated health status revealed a gradient across disease severity groups. 66.7% of mild PAD patients (n = 18) reported “fair or poor” health status, compared to 40.7% of those with moderate PAD (n = 27), and 54.8% in the severe PAD group (n = 31) (Fig. 1 A). Mental health challenges lasting for 14 or more days were reported by 16.7% of mild PAD patients, compared to 33.3% of patients with moderate PAD and 22.6% of those with severe PAD (Fig. 1 B). The evaluation of physical health revealed that 38.9% of mild PAD patients (n = 7) experienced poor physical health for 14 or more days, a slight increase to 44.4% for moderate PAD patients (n = 12), and nearly half, 48.4%, for severe PAD patients (n = 15), reported prolonged periods of poor physical health (Fig. 1 C). There was no statistically significant difference across the disease severity groups. The impact of PAD on patients' daily activities was profound across all severity groups. The majority of patients reported limitations in activities due to health problems with 88.9% in the mild PAD group (n = 16), 92.0% in the moderate PAD group (n = 23), and 71.0% in the severe PAD group (n = 22). Patients across all severity groups reported similar mean numbers of days with poor physical health (13.4 for mild vs. 13.1 for moderate vs. 13.6 for severe PAD) and mental health (5.5 for mild vs. 10.6 for moderate vs. 8.0 for severe PAD) within the past 30 days. The long-term impact on daily activities, as measured by the number of months that activities were limited by health issues, varied widely with patients with mild PAD reporting a mean of 32.0 months, patients with moderate PAD reporting a mean of 111.5 months, and patients with severe PAD reporting a mean of 52.2 months. Pain was reported as a key factor limiting usual activities for an average of 11.3, 9.4, and 9.0 days in the mild, moderate, and severe PAD groups, respectively. The percentage of patients needing assistance with personal care varied across severity groups, with 5.6% of mild PAD patients, 14.8% of moderate PAD patients, and 13.3% of severe PAD patients reporting this need. Assistance with routine needs was consistently reported by patients across severity levels, with 50.0% in the mild (n = 9), 51.9% in the moderate (n = 14), and 36.7% in the severe (n = 11) groups. Emotional well-being, measured by days felt sad or depressed, was variable between groups, with a slightly higher mean of 9.5 days in the moderate PAD group compared to 4.3 and 4.8 days in the mild and severe groups, respectively. Similarly, anxiety levels were similar across severity groups, with the average number of days feeling anxious being 8.9 for mild, 12.6 for moderate, and 7.0 for severe PAD. Sleep disturbances, measured by the number of days not feeling rested or having enough sleep, also showed no significant difference, with an average of 14.9 days for mild, 15.2 for moderate, and 11.4 for severe PAD patients. We compared the core HRQoL-14 questions between primary PAD patients (n = 76) and secondary PAD patients (n = 7). 55.2% of primary PAD patients reported “fair or poor” health status, compared to 28.5% of secondary PAD patients (p = 0.18) (Fig. 2 A). In the mental health domain, 34.2% of primary PAD patients reported challenges lasting 14 or more days, whereas only 14.3% of secondary PAD patients reported similar challenges (p = 0.28) (Fig. 2 B). Physical health assessments revealed that 51.3% of primary PAD patients experienced poor physical health for 14 or more days, compared to 28.5% of secondary PAD patients (p = 0.25) (Fig. 2 C). Among CVID patients, we compared the core HRQoL-14 responses between complicated (n = 44) and uncomplicated (n = 20) CVID patients. Patients with complicated CVID were more likely to rate their health as "fair" or "poor" (56.8%, n = 25) compared to those with uncomplicated CVID (40%, n = 8) (p = 0.21) (Fig. 3 A). Mental health challenges lasting for 14 or more days were reported by 31.8% of patients with complicated CVID, compared to a slightly higher 40% of those with uncomplicated CVID (p = 0.52) (Fig. 3 B). The evaluation of physical health revealed that 47.7% of patients with complicated CVID experienced poor physical health for 14 or more days, compared to a prolonged period reported by 55% of those with uncomplicated CVID (p = 0.59) (Fig. 3 C). Although trends in the data suggest a relationship between increased disease severity and poorer HRQoL— especially in terms of physical health and fair or poor self-rated health status—the differences did not reach statistical significance, likely due to sample size. Similarly, when we stratified the analyses by therapies received and genetic testing, no statistically significant differences were observed when comparing those with and without immunoglobulin replacement therapy (IgRT) (Supplemental Figure S1), having received immunomodulator therapy (Supplemental Figure S2), or having an identified genetic etiology (Supplemental Figures S3). This may imply that the diagnosis of PAD itself, irrespective of the severity level, imposes a substantial burden on the HRQoL of patients. We further evaluated the core HRQoL-14 responses between primary PAD patients with (n = 41) and without (n = 35) autoinflammatory features. In the mental health domain, 78% of patients with autoinflammatory features reported challenges lasting 14 or more days, significantly higher than the 54.3% of patients without these features (p = 0.02) (Fig. 4 B). A similar trend was noted in the other two domains. Patients with autoinflammatory features were more likely to rate their health as "fair" or "poor" (61%) compared to those without autoinflammatory features (48.6%) (p = 0.28) (Fig. 4 A). Physical health assessments indicated that 53.7% of patients with autoinflammatory features experienced poor physical health for 14 or more days, compared to 48.6% of those without (p = 0.66) (Fig. 4 C). However, these differences were not statistically significant. HRQoL is lower in PAD patients compared to healthy controls We conducted a comparative analysis of HRQoL-14 Healthy Days Measure questionnaire responses between PAD patients (n = 83) and a control group of the general population (n = 801,582) from CDC-BRFSS data from a similar geographic area (Table 3 ). Patients with PAD were more likely to evaluate their health as “fair” or “poor” (53%, n = 44), which was significantly higher than the 12.0% in the CDC-BRFSS comparator group (n = 96,190), indicating a marked impact of PAD on self-perceived health (p < 0.0001) (Fig. 5 A). In the mental health domain, 24.1% of PAD patients (n = 20) reported challenges lasting 14 or more days, which was significantly more than the 14.7% in the CDC-BRFSS comparator group (n = 117,833) (p = 0.02) (Fig. 5 B). Physical health assessments further illustrated the PAD patients' burden, with 44.6% (n = 37) experiencing poor physical health for 14 or more days, notably higher than the 8.0% in the CDC-BRFSS comparator group (n = 64,127) (p < 0.0001) (Fig. 5 C). Table 3 Comparison of HRQoL-14 responses among PAD patients and BRFSS respondents. Sample Size Cases No. Proportion (95% CI) P-value Fair or poor self-rated health status (% [n]) PAD 83 44 53.0% (42.3%-63.8%) < 0.0001 CDC-BRFSS Controls 801,582 96,190 12.0% (10.7%-13.5%) Mental health not good for ≥ 14 days (% [n]) PAD 83 20 24.1% (14.9%-33.3%) 0.02 CDC-BRFSS Controls 801,582 117,833 14.7% (13.6%-15.9%) Physical health not good for ≥ 14 days (% [n]) PAD 83 37 44.6% (33.9%-55.3%) < 0.0001 CDC-BRFSS Controls 801,582 64,127 8.0% (7.3%-8.7%) DISCUSSION In our study, we evaluated the HRQoL using the CDC HRQoL-14 Healthy Days Measure questionnaire among patients with mild, moderate, and severe primary PAD. Additionally, we compared HRQoL across several strata including primary and secondary PAD, complicated and uncomplicated CVID patients, presence and absence of autoinflammatory features, and between those receiving or not receiving immunoglobulin replacement and immunomodulator therapies. We also compared the HRQoL of PAD patients with that of the general population, utilizing data from the CDC-BRFSS. Consistent with prior research, we observed that PAD has a significant negative impact on patients' quality of life when compared to the general population. Our assessment of HRQoL among PAD patients revealed that the burden of the disease on QoL was evident across all levels of disease severity. Our analysis did not reveal a direct correlation between increasing severity and lower HRQoL scores; instead, it revealed a more complex pattern. While a high percentage of mild PAD patients reported fair or poor self-rated health status, this did not linearly increase with disease severity. Despite nearly half of the severe PAD group reporting extended periods of poor physical health, this percentage was not significantly higher than that reported by the mild group. Activity limitations, another key indicator of HRQoL, were reported by a substantial majority of patients across all severity groups. Moreover, the need for assistance with personal care and routine needs, as well as emotional and sleep disturbances, showed no significant variation across the disease severity spectrum. Comparing primary and secondary PAD patients, we found that primary PAD patients reported worse HRQoL outcomes. A higher proportion of primary PAD patients rated their health as "fair or poor" and experienced prolonged periods of poor physical and mental health compared to secondary PAD patients. Notably, primary PAD patients with autoinflammatory features exhibited significantly worse mental health outcomes, with 78% reporting challenges lasting 14 or more days, compared to 54.29% of those without autoinflammatory features. While trends in physical health and overall health ratings followed a similar pattern, these differences were not statistically significant, which may have been limited by sample size. Similarly, our extended analysis, including stratifications based on immunoglobulin replacement therapy, immunomodulator therapy, and identified genetic etiology, did not reveal statistically significant differences across the three domains. These findings suggest that the diagnosis of PAD itself, regardless of severity, places a substantial burden on patients' HRQoL. This indicates that factors beyond disease severity, such as psychosocial or environmental factors, psychological resilience, and coping mechanisms developed over time, may significantly influence quality of life. These factors could potentially buffer the impact of disease progression on perceived well-being, highlighting the need for comprehensive care approaches that address not only the physical but also the mental and social aspects of living with PAD. The comparison of HRQoL between PAD patients and the comparator population from the BRFSS data further highlights the significant impact of PAD on patients' lives. PAD patients were more than four times as likely to report fair or poor self-rated health compared to the CDC-BRFSS comparator group, a difference that was highly significant. PAD also had a substantial negative impact on mental health, with nearly a quarter reporting poor mental health for two weeks or more, a rate significantly higher than in the BRFSS data. Similarly, the physical domain was severely affected, with PAD patients experiencing poor physical health for extended periods at a rate more than five times higher than that of the general population. These findings highlight the need for targeted interventions in PAD patients, designed to mitigate the extensive impact of both mental and physical heath domains, and address the broad and complex needs that extend beyond the clinical diagnosis of PAD. While treatments such as immunoglobulin replacement therapy (IgRT), antibiotic prophylaxis, and in severe cases, hematopoietic stem cell transplantation (HSCT), have notably improved survival rates for patients with PAD, patients still continue to face challenges in their physical and mental health. Therefore, assessing the HRQoL is critical for understanding the comprehensive impact of PAD on patients' daily lives and overall well-being. Of note, here we did not see QoL benefit from immunomodulator therapy. These data may suggest that additional or alternative targeted approaches are needed. Future work is needed to investigate these outcomes by specific immunomodulator therapy type, duration, and targeted treatment approach. While several studies have investigated HRQoL in adults and pediatric patients with IEI, research has yet to focus on adult patients with PAD or to draw comparisons with healthy controls. Generally, data from these studies indicate that IEI patients have a significantly poorer overall health status and self-rated health when compared with those suffering from other chronic diseases.( 16 ) Research reveals that IEI patients experience more severe mental health issues, such as depression, isolation, and anxiety, than those observed in the general population.( 14 ) These findings are consistent with previous research that has established psychosocial factors as substantial determinants of the incidence, QoL, and mortality rates associated with chronic illnesses.( 31 , 32 ) There were several limitations to our study. Although we assessed a considerable number of PAD patients, the cohort was predominantly female and non-Hispanic White. Thus, the external validity of our findings might be limited, highlighting the need for future research involving PAD patients of more diverse backgrounds who are matched to healthy controls.( 33 , 34 ) Furthermore, the small sample size and the cross-sectional design of the study may restrict the generalizability of our findings and our ability to establish causality. The reliance on self-reported measures, while insightful for understanding patient experiences, could introduce response biases. Additionally, the recruitment of participants from a single center might not accurately represent the wider PAD patient population. Despite these limitations, our findings provide an essential foundation for future research aimed at enhancing the QoL for individuals with PAD. Further studies with larger, more diverse populations and longitudinal designs are needed to clarify the long-term impacts of PAD on HRQoL and validate the interventions that may improve outcomes for these patients. In conclusion, this study provides insights into the significant impact of PAD on HRQoL across all severity levels, demonstrating the necessity for care strategies that include mental and social health support alongside medical management. The findings also stress the importance of interventions tailored to all severity levels, not limited to those classified as a clinically severe phenotype. Though progress has been achieved in treating PAD, there is a heightened need to focus on improving patients' health-related quality of life. This requires creating strong methods for evaluating HRQoL and meeting the psychological and social needs of those with PAD. Future research, with a focus on long-term studies and a broader, more inclusive, demographic is needed to develop effective interventions that enhance quality of life for all patients with PAD. Abbreviations PAD predominantly antibody deficiency HRQoL health–related quality of life CDC centers for disease control and prevention BRFSS behavioral risk factor surveillance system IVIG intravenous immunoglobulin SCIG subcutaneous immunoglobulin CVID common variable immunodeficiency SAD specific antibody deficiency IgG immunoglobulin G IRB institutional review board HSCT hematopoietic stem cell transplantation IgRT immunoglobulin replacement therapy ANOVA analysis of variance Declarations Author Contribution S.B. study conception and design. A.E. and S.B. wrote the main manuscript text. B.Z. and A.E. analyzed the data and prepared the figures. J. S. H., M.T., and A.P. collected, extracted, cleaned, and analyzed the data. M.O., N.S., D.V.D and J.R.F. interpreted the results. All authors reviewed the manuscript. Funding/Support Sara Barmettler is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number K23AI163350 and a faculty development award from the American Academy of Allergy Asthma & Immunology (AAAAI). Jocelyn R. Farmer was supported by a faculty development award from the American Academy of Allergy Asthma & Immunology (AAAAI) and the National Institute on Minority Health and Health Disparities of the National Institute of Health under award number R01MD017816. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Disclosure of Conflicts of Interest: Jocelyn R. Farmer is an ongoing consultant for Pharming and has received investigator-initiated research grants from Pfizer, Bristol Myers Squibb, and Pharming with no direct relation to the work presented. Daniel DiGiacomo has received consulting fees from BASF. References Gathmann B, Grimbacher B, Beaute J, Dudoit Y, Mahlaoui N, Fischer A et al. The European internet-based patient and research database for primary immunodeficiencies: results 2006–2008. Clin Exp Immunol. 2009;157(Suppl 1):3–11. 10.1111/j.1365-2249.2009.03954.x . PMID: 19737289. Picard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, et al. International union of immunological societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol. 2018;38:96–128. 10.1007/s10875-017-0464-9 . Durandy A, Kracker S, Fischer A. Primary antibody deficiencies. Nat Rev Immunol. 2013;13:519–33. 10.1038/nri3466 . Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah S, Chapel H. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 2010;125:1354–e601354. 10.1016/j.jaci.2010.02.040 . Bousfiha A, Jeddane L, Picard C, Ailal F, Bobby Gaspar H, Al-Herz W, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2018;38:129–43. 10.1007/s10875-017-0465-8 . Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186–205. e1-78. Cheraghi T, Kalantari A, Shabestari MS, Abolhassani H, Eibel H, Hammarström L. Inborn Errors of Immunity. 1st ed. Academic; 2021. 10.1016/B978-0-12-821028-4.00006-3 . Bakas T, Mclennon SM, Carpenter JS, Buelow JM, Otte JL, Hanna KM, et al. Systematic review of health-related quality of life models. Health Qual Life outcomes. 2012;10:1–12. 10.1186/1477-7525-10-134 . Mandzuk LL, McMillan DE. A concept analysis of quality of life. J Orthop Nurs. 2005;9:12–8. 10.1016/j.joon.2004.11.001 . Peshko D, Kulbachinskaya E, Korsunskiy I, Kondrikova E, Pulvirenti F, Quinti I, et al. Health-related quality of life in children and adults with primary immunodeficiencies: a systematic review and meta-analysis. J Allergy Clin Immunology: Pract. 2019;7:1929–e575. 10.1016/j.jaip.2019.02.013 . Ravens-Sieberer U, Erhart M, Wille N, Wetzel R, Nickel J, Bullinger M. Generic health-related quality-of-life assessment in children and adolescents: methodological considerations. PharmacoEconomics. 2006;24:1199–220. 10.2165/00019053-200624120-00005 . Kuburovic NB, Pasic S, Susic G, Stevanovic D, Kuburovic V, Zdravkovic S, et al. Health-related quality of life, anxiety, and depressive symptoms in children with primary immunodeficiencies. Patient Prefer Adherence. 2014;8:323–30. 10.2147/PPA.S58040 . PMID: 24672289. PMC: PMC3962398. Varni JW, Burwinkle TM, Lane MM. Health-related quality of life measurement in pediatric clinical practice: an appraisal and precept for future research and application. Health Qual Life outcomes. 2005;3:1–9. 10.1186/1477-7525-3-34 . Xiao N, Huang X, Zang W, Kiselev S, Bolkov MA, Tuzankina IA, Chereshnev VA. Health-related quality of life in patients with inborn errors of immunity: a bibliometric analysis. Front Immunol. 2024;15:1371124. 10.3389/fimmu.2024.1371124 . Jolles S, Orange JS, Gardulf A, Stein MR, Shapiro R, Borte M, Berger M. Current treatment options with immunoglobulin G for the individualization of care in patients with primary immunodeficiency disease. Clin Exp Immunol. 2015;179(2):146–60. 10.1111/cei.12485 . PMID: 25384609; PMCID: PMC4298393. Tabolli S, Giannantoni P, Pulvirenti F, La Marra F, Granata G, Milito C, et al. Longitudinal study on health-related quality of life in a cohort of 96 patients with common variable immune deficiencies. Front Immunol. 2014;5:605. 10.3389/fimmu.2014.00605 . Routes J, Costa-Carvalho BT, Grimbacher B, Paris K, Ochs HD, Filipovich A, et al. Health-related quality of life and health resource utilization in patients with primary immunodeficiency disease prior to and following 12 months of immunoglobulin G treatment. J Clin Immunol. 2016;36:450–61. 10.1007/s10875-016-0279-0 . Nijhof LN, van Brussel M, Pots EM, van Litsenburg RR, van de Putte EM, van Montfrans JM, et al. Severe fatigue is common among pediatric patients with primary immunodeficiency and is not related to disease activity. J Clin Immunol. 2021;41:1198–207. 10.1007/s10875-021-01013-7 . Manusama OR, van Beveren NJ, van Hagen PM, Drexhage HA, Dalm VA. Psychological symptoms in primary immunodeficiencies: a common comorbidity? J Clin Immunol. 2022;42:695-8. 10.1007/s10875-022-01207-7 . PMID: 35043302. Sowers KL, Gayda-Chelder CA, Galantino ML. Self-reported cognitive impairment in individuals with Primary Immunodeficiency Disease. Brain Behav Immunity-Health. 2020;9:100170. 10.1016/j.bbih.2020.100170 . Rozanski A, Blumenthal JA, Davidson KW, Saab PG, Kubzansky L. The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. J Am Coll Cardiol. 2005;45:637–51. 10.1016/j.jacc.2004.12.005 . Suls J, Bunde J. Anger, anxiety, and depression as risk factors for cardiovascular disease: the problems and implications of overlapping affective dispositions. psychol Bull. 2005;131:260. 10.1037/0033-2909.131.2.260 . McCallum SM, Batterham PJ, Calear AL, Sunderland M, Carragher N, Kazan D. Associations of fatigue and sleep disturbance with nine common mental disorders. J Psychosom Res. 2019;123:109727. 10.1016/j.jpsychores.2019.05.005 . Centers for Disease Control and Prevention Measuring Healthy Days. Population assessment of health-related quality of life. Atlanta Ga CDC Apr. 2024. https://archive.cdc.gov/#/details?url=https://www.cdc.gov/hrqol/index.htm . Pickens CM, Pierannunzi C, Garvin W, Town M. Surveillance for Certain Health Behaviors and Conditions Among States and Selected Local Areas - Behavioral Risk Factor Surveillance System, United States, 2015. MMWR Surveill Summ. 2018;67(9):1–90. Iachan R, Pierannunzi C, Healey K, Greenlund KJ, Town M. National weighting of data from the Behavioral Risk Factor Surveillance System (BRFSS). BMC Med Res Methodol. 2016;16(1):155. Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. International Consensus Document (ICON): Common Variable Immunodeficiency Disorders. J Allergy Clin Immunol Pract. 2016;4(1):38–59. Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, et al. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol. 2020;40(1):66–81. Tandon M, DiGiacomo DV, Zhou B, Hesterberg P, Rosenberg CE, Barmettler S, Farmer JR. Response to SARS-CoV-2 initial series and additional dose vaccine in pediatric patients with predominantly antibody deficiency. Front Immunol. 2023;14:1217718. 10.3389/fimmu.2023.1217718 . PMID: 37575247; PMCID: PMC10413262. Zhang AM, Elmoursi A, DiGiacomo DV, Zhou B, Tandon M, Hong JS, Yang NJ, Ong MS, Dighe AS, Berrios C, Poznansky MC, Iafrate AJ, Naranbhai V, Balazs A, Pillai S, Farmer JR, Barmettler S. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency. J Allergy Clin Immunol Glob. 2024;3(2):100234. 10.1016/j.jacig.2024.100234 . PMID: 38544577; PMCID: PMC10965812. Santos T, de Matos MG, Simões C, Leal I. do Céu MaChado M. (Health-related) quality of life and psychosocial factors in adolescents with chronic disease: A systematic literature review. Int J Adolesc Med Health. 2017;31:20170037. 10.1515/ijamh-2017-0037 . Sahle BW, Chen W, Melaku YA, Akombi BJ, Rawal LB, Renzaho AM. Association of psychosocial factors with risk of chronic diseases: A nationwide longitudinal study. Am J Prev Med. 2020;58:e39–50. 10.1016/j.amepre.2019.09.007 . Hayes DK, Greenlund KJ, Denny CH, Neyer JR, Croft JB, Keenan NL. Racial/ethnic and socioeconomic disparities in health-related quality of life among people with coronary heart disease, 2007. Prev Chronic Dis. 2011;8(4):A78. Epub 2011 Jun 15. PMID: 21672402; PMCID: PMC3136984. Wallander JL, Fradkin C, Elliott MN, Tortolero S, Cuccaro P, Schuster MA. Racial/ethnic disparities in health-related quality of life and health status across pre-, early-, and mid-adolescence: a prospective cohort study. Qual Life Res . 2019;28:1761–1771. 10.1007/s11136-019-02157-1 . PMID: 30788576. Additional Declarations No competing interests reported. Supplementary Files SUPPLEMENT.docx Cite Share Download PDF Status: Published Journal Publication published 07 Aug, 2024 Read the published version in Journal of Clinical Immunology → Version 1 posted Editorial decision: Revision requested 07 Jul, 2024 Reviews received at journal 06 Jul, 2024 Reviewers agreed at journal 01 Jul, 2024 Reviewers invited by journal 30 Jun, 2024 Editor assigned by journal 21 Jun, 2024 Submission checks completed at journal 21 Jun, 2024 First submitted to journal 20 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4612913","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":323714393,"identity":"8f005164-7c5d-4ba6-8c74-f86a1ffb267b","order_by":0,"name":"Ahmed Elmoursi","email":"","orcid":"","institution":"Massachusetts General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Elmoursi","suffix":""},{"id":323714394,"identity":"6e380e47-7e56-4ca8-a72e-d479104bbae3","order_by":1,"name":"Baijun Zhou","email":"","orcid":"","institution":"Massachusetts General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Baijun","middleName":"","lastName":"Zhou","suffix":""},{"id":323714395,"identity":"4c0c03cf-5b88-4a6c-babc-b7ca86a315b6","order_by":2,"name":"Mei-Sing Ong","email":"","orcid":"","institution":"Harvard Medical School, Harvard Pilgrim Health Care Institute","correspondingAuthor":false,"prefix":"","firstName":"Mei-Sing","middleName":"","lastName":"Ong","suffix":""},{"id":323714396,"identity":"374837e8-b46f-4f75-9e0e-07e97036dbbf","order_by":3,"name":"Joseph S. Hong","email":"","orcid":"","institution":"Massachusetts General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Joseph","middleName":"S.","lastName":"Hong","suffix":""},{"id":323714397,"identity":"495e4e71-2d7e-4551-82bd-ab5bceef98e1","order_by":4,"name":"Andrew Pak","email":"","orcid":"","institution":"Massachusetts General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Andrew","middleName":"","lastName":"Pak","suffix":""},{"id":323714399,"identity":"f1d26286-7a92-4a71-bb20-313daef17731","order_by":5,"name":"Megha Tandon","email":"","orcid":"","institution":"Massachusetts General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Megha","middleName":"","lastName":"Tandon","suffix":""},{"id":323714400,"identity":"49fde82d-4f97-4380-94cd-944e2868d171","order_by":6,"name":"Natalia Sutherland","email":"","orcid":"","institution":"Massachusetts General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Natalia","middleName":"","lastName":"Sutherland","suffix":""},{"id":323714401,"identity":"ce850e7a-591b-488a-aec5-bcf076c5261a","order_by":7,"name":"Daniel V. DiGiacomo","email":"","orcid":"","institution":"Hackensack Meridian School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"V.","lastName":"DiGiacomo","suffix":""},{"id":323714406,"identity":"f51cb251-62ca-437a-8900-d97375bdad67","order_by":8,"name":"Jocelyn R. Farmer","email":"","orcid":"","institution":"Beth Israel Lahey Health","correspondingAuthor":false,"prefix":"","firstName":"Jocelyn","middleName":"R.","lastName":"Farmer","suffix":""},{"id":323714409,"identity":"04f6d132-691e-400d-9466-6ba5cfeb7572","order_by":9,"name":"Sara Barmettler","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABHUlEQVRIiWNgGAWjYDACCSjNx8DA+ICB4QCDAYTPDMQJ+LQYSLABVRmQrIVNgigt8rObn326UfGnjo2991nVjV93GMzZzz6T+LnHmoGfPccAmxaDO8eMZ+ecAdrCc9zsdm7fMwbLnnQzyZ5n6QySPW+wa5FIMGbObQNqkUhju53bc5jB4EAaswHPASDjBnZb5Gekf2bO/QfUIv+MrRis5fwzZsM/QC32OLQw3MgB2tIAsoWNjTnnB8jwNMbHYFskcPnlTDFzzjFjyTaeNGbp3IbDPAY3njE+ljmQziNx5lkB9hBr38ycUyPHz89+jPFzzp/Dcgbn0xgOvjlgLcffnrwBq8NQAGMbAw+MzYNPIRL4Q6S6UTAKRsEoGFEAABPfXu2aBp9JAAAAAElFTkSuQmCC","orcid":"","institution":"Massachusetts General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Sara","middleName":"","lastName":"Barmettler","suffix":""}],"badges":[],"createdAt":"2024-06-20 15:51:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4612913/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4612913/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10875-024-01781-y","type":"published","date":"2024-08-07T15:58:05+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60616920,"identity":"b4e4a1fa-b098-4e26-a86d-50d765e996bb","added_by":"auto","created_at":"2024-07-18 20:26:36","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":63368,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePercentage of poor self-rated health status, mental health, and physical health among primary PAD patients by clinical severity.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe figure represents the distribution of self-rated health status: A) Fair or poor self-rated health status, B) Mental health not good for ≥14 days, and C) Physical health not good for ≥14 days, segregated by disease severity. The vertical axis indicates the percentage of respondents, and the horizontal axis classifies the severity of PAD into mild (green bar; n=18), moderate (yellow bar; n=27), and severe (red bar; n=31) PAD adult patients. Each bar indicates the proportion of individuals who reported their health status. Error bars represent the 95% confidence interval of the proportion of respondents. Although a trend of increased poor health status with greater disease severity is observed, the differences did not reach statistical significance.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4612913/v1/efec7a748c0c199ba8f6fbef.jpeg"},{"id":60616919,"identity":"9c5b14d1-a8c2-4dbb-8d84-ccf3f0f7530b","added_by":"auto","created_at":"2024-07-18 20:26:36","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":48084,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePercentage of poor self-rated health status, mental health, and physical health among primary PAD patients compared to secondary PAD.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe figure represents the distribution of self-rated health status: A) Fair or poor self-rated health status, B) Mental health not good for ≥14 days, and C) Physical health not good for ≥14 days, compared between adult patients with primary PAD (red bar; n=76) and secondary PAD (purple bar; n=7). Each bar indicates the proportion of individuals who reported their health status. Error bars represent the 95% confidence interval of the proportion of respondents. Although primary PAD patients show a trend of worse health status compared to secondary PAD patients, the differences did not achieve statistical significance.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4612913/v1/297b68ab7aaca0fa3660bb42.jpeg"},{"id":60616918,"identity":"c417b4e2-0925-4934-aedd-f28112fd798f","added_by":"auto","created_at":"2024-07-18 20:26:36","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":55991,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePercentage of poor self-rated health status, mental health, and physical health among CVID patients by complication status.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe figure represents the distribution of self-rated health status: A) Fair or poor self-rated health status, B) Mental health not good for ≥14 days, and C) Physical health not good for ≥14 days, compared between complicated (maroon bar; n=44) and uncomplicated (cyan bar; n=20) CVID patients. Each bar indicates the proportion of individuals who reported their health status. Error bars represent the 95% confidence interval of the proportion of respondents.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4612913/v1/2a15de9576fdc8b90e948cbc.jpeg"},{"id":60618073,"identity":"d44399e5-069b-4b32-b92a-63ae51d7d528","added_by":"auto","created_at":"2024-07-18 20:34:36","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":347418,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePercentage of poor self-rated health status, mental health, and physical health among primary PAD patients by autoinflammatory features.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe figure represents the distribution of self-rated health status: A) Fair or poor self-rated health status, B) Mental health not good for ≥14 days, and C) Physical health not good for ≥14 days, segregated by presence of autoinflammatory features. The vertical axis indicates the percentage of respondents, and the horizontal axis differentiates between PAD patients with (maroon bar; n=41) and without (cyan bar; n=35) autoinflammatory features. Each bar shows the proportion of individuals reporting their health status. Error bars indicate the 95% confidence interval of the proportion of respondents. A significant difference in mental health status is noted (*p\u0026lt;0.05), with worse mental health observed in patients with present autoinflammatory features.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4612913/v1/28d5b06cd83c16a166d2a6bd.jpeg"},{"id":60618072,"identity":"e8c72da8-ff6b-4953-a2de-b08c5d62ce44","added_by":"auto","created_at":"2024-07-18 20:34:36","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":427420,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePercentage of poor self-rated health status, mental health, and physical health among PAD patients compared to CDC-BRFSS data controls.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe figure represents the distribution of self-rated health status: A) Fair or poor self-rated health status, B) Mental health not good for ≥14 days, and C) Physical health not good for ≥14 days, compared between adult patients with PAD (red bar; n=83) and control data derived from the CDC’s BRFSS data surveying the general population (gray bar; n=801,582). Each bar indicates the proportion of individuals who reported their health status. HC stands for healthy controls from CDC-BRFSS data. Error bars represent the 95% confidence interval of the proportion of respondents. *p\u0026lt;0.05. The results demonstrate that PAD patients have significantly lower HRQoL across all measured domains compared to the control group.\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4612913/v1/f7a3cdfb632685bd21e50b20.jpeg"},{"id":62298591,"identity":"81ef7b77-c465-418c-8948-c5c6c6d0a2a9","added_by":"auto","created_at":"2024-08-12 16:15:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1719388,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4612913/v1/ab6f235d-96d0-44ab-91d0-decfc2f6ef1d.pdf"},{"id":60616923,"identity":"91ddc72d-99d1-4b30-a8aa-4952117156ff","added_by":"auto","created_at":"2024-07-18 20:26:36","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":178358,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENT.docx","url":"https://assets-eu.researchsquare.com/files/rs-4612913/v1/83a48288a62e81513e741a89.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Cross-Sectional Study of Health-Related Quality of Life in Patients with Predominantly Antibody Deficiency ","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePredominantly antibody deficiency (PAD) is the most frequently diagnosed inborn error of immunity (IEI) and the most common primary immunodeficiency disorder worldwide.(\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Patients with PAD are susceptible to recurrent infections due to reduced antibody levels and/or inadequate vaccination responses.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) However, the impact of PAD extends beyond recurrent infections; affected individuals often face a spectrum of comorbidities, including autoimmune diseases and lymphoproliferative disorders, which can contribute to progressive end-organ damage and a diminished life expectancy.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe concept of health-related quality of life (HRQoL) is becoming increasingly recognized as an important metric for evaluating patient well-being and for guiding therapeutic choices in both clinical and research settings.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) HRQoL captures a comprehensive, multifaceted evaluation of an individual's physical, psychological, emotional, and social functioning. This in turn reflects a wide-ranging and complex domain of interest among diverse stakeholders including healthcare providers, researchers, policymakers, and families.(\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) Increasing evidence positions HRQoL as an essential indicator for assessing treatment effectiveness and the overall health of those with chronic conditions. This approach extends beyond traditional clinical measures such as survival, adverse events, and death rates to offer a holistic view of the effects of disease and treatment on a patient's life from their own perspective.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eStudies have shown that HRQoL measurements, when tailored to specific conditions, provide a more precise evaluation of the impacts of medical interventions on patient lives when compared to general clinical assessments. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) This approach facilitates the identification of various health determinants and guides the development of personalized treatment, management, and preventive strategies, aligning with healthcare\u0026rsquo;s ultimate goal of enhancing QoL while also prolonging lives. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe principal strategy for both prophylaxis and management of PAD is the administration of immunoglobulin G (IgG) replacement, either intravenously (IVIG) or subcutaneously (SCIG). This therapeutic approach has proven to be both effective and safe in reducing the incidence and severity of infections in PAD patients.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Despite this, patients continue to face ongoing challenges, such as recurrent infections, autoimmune and lymphoproliferative complications, and the need for frequent acute care visits. These challenges are attributed to the chronic nature of PAD, treatment side effects, and the complexities of their care management. This limits patients\u0026rsquo; social and physical activities (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), contributing to an increased risk of fatigue (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), depression (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), anxiety (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), cardiovascular diseases, cancer, sleep disorders, and mental health conditions (\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), which may severely affect their psychological and physical health, and consequently, reduce their overall quality of life (QoL).\u003c/p\u003e \u003cp\u003eDespite the progress in treatment modalities that have improved survival rates for individuals with PAD, the impact of PAD on HRQoL has not been thoroughly researched. Therefore, we sought to assess HRQoL in PAD by utilizing the Centers for Disease Control (CDC) Health-Related Quality of Life (HRQoL)-14 Healthy Days Measure questionnaire (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), and to compare the HRQoL of PAD patients with that of the general population, utilizing data from the CDC's Behavioral Risk Factor Surveillance System (BRFSS).(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis cross-sectional observational study was designed to assess the HRQoL in patients diagnosed with PAD. Adult PAD patients (age\u0026thinsp;\u0026ge;\u0026thinsp;18 years) were consented at Mass General Brigham (MGB). Participants voluntarily completed the Centers for Disease Control (CDC) HRQoL-14 Healthy Days Measure questionnaire (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) during routine visits or at intermittent time points. This was conducted under an Institutional Review Board (IRB) approved protocol (#2018P002713) between September 24, 2019, and February 12, 2024. The diagnoses of PAD were confirmed through manual chart review by a clinical immunologist, and met consensus definitions.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eA total of 83 patients with PAD were included. HRQoL-14 Healthy Days Measure is a self-report questionnaire designed to assess HRQoL among adult participants. It contains 14 items distributed across two primary dimensions: Mental Health (MH) (4 items), and Physical Health (PH) (10 items). Some items are assessed on a categorical scale and others require respondents to provide a continuous measure, such as reporting the number of unhealthy days they have experienced within the past 30 days. Taken together, these measures indicate a patient\u0026rsquo;s health status with a higher count suggesting a poorer health condition.\u003c/p\u003e \u003cp\u003eSupplementary sections delve into specifics such as activity limitations and health symptoms such as pain, depression, anxiety, sleep disorders, and energy levels. It also inquires about respondents' recent health conditions and any limitations to their activities. The completion of the questionnaire typically requires no more than five minutes. The total and dimensional scores are interpreted directly, with no need for transformation to a percentage of a maximum possible score. For items with missing responses, the CDC provides guidelines on how to handle incomplete data based on the specific requirements of the analysis.(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) The questionnaire was originally developed in English and is publicly available for use.\u003c/p\u003e \u003cp\u003ePatients with PAD were subclassified as mild (Primary hypogammaglobulinemia, IgG subclass deficiency, and specific antibody deficiency [SAD]), moderate (uncomplicated common variable immunodeficiency [CVID]), and severe (complicated PAD defined as a presence of co-occurring autoinflammatory clinical features (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)), as previously published.(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) Patients with confounding variables at the time of immunodeficiency diagnosis (e.g., clonal lymphocyte population or ongoing immunosuppression without the potential for discontinuation) were considered to be secondary PAD. We compared the responses across the three severity levels among primary PAD patients, and further we compared responses from PAD patients with data from the CDC-initiated Behavioral Risk Factor Surveillance System (BRFSS), which included HRQOL-14 responses from a control comparator group of the general population in the Boston area, consisting of 801,582 respondents, in 2021.(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eData were collected on patient demographics including age, gender, race, and specific PAD diagnoses. Information regarding clinical characteristics and disease severity was gathered through patient medical records. Descriptive statistics were used to summarize the sample characteristics, with mean values described for continuous variables and frequencies and percentages for categorical variables. We used a two-proportion Z-test to compare the responses from PAD patients in our study with the CDC-BRFSS data. Chi-square tests and analyses of variance (ANOVA) were used to compare the responses across three severity levels among PAD patients. Statistical analyses were completed with SAS 9.4 (SAS Institute, Cary, NC) and Prism Version 7.01 (Reston, VA). A two-tailed p-value of \u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePAD patient demographics\u003c/h2\u003e \u003cp\u003eThis cross-sectional observational study evaluated 83 adult patients diagnosed with PAD using the CDC HRQoL-14 Healthy Days Measure questionnaire. Among these patients, 91.6% (n\u0026thinsp;=\u0026thinsp;76) had primary PAD and 8.4% (n\u0026thinsp;=\u0026thinsp;7) had secondary PAD. The average age of participants was 54.8 years, with a standard deviation (SD) of 15.4 years. 71% were female and 97.6% were non-Hispanic White. The most common type of PAD was complicated Common Variable Immunodeficiency (CVID) (e.g. CVID with autoinflammatory features or a more severe immunophenotype), observed in 53% of patients (n\u0026thinsp;=\u0026thinsp;44), followed by uncomplicated CVID, which constituted 24.1% (n\u0026thinsp;=\u0026thinsp;20) of the cases. Primary hypogammaglobulinemia was present in 8.4% (n\u0026thinsp;=\u0026thinsp;7) of participants, secondary hypogammaglobulinemia in 8.4% (n\u0026thinsp;=\u0026thinsp;7), specific antibody deficiency accounted for in 3.6% (n\u0026thinsp;=\u0026thinsp;3), and IgG subclass deficiency accounted for 2.4% (n\u0026thinsp;=\u0026thinsp;2) of the PAD types within our study population (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Primary PAD patients were stratified by their disease severity; 23.7% (n\u0026thinsp;=\u0026thinsp;18) had mild PAD, 35.5% (n\u0026thinsp;=\u0026thinsp;27) had moderate PAD, and 40.8% (n\u0026thinsp;=\u0026thinsp;31) had severe PAD. This sample was representative of our overall MGB cohort of patients with PAD in terms of age, race/ethnicity, and disease distribution (Table S1).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient demographics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePredominantly antibody deficiency, n\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAverage age (years, [std])\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.8 (15.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale (% [n])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.9 (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale (% [n])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.1 (59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRace (% [n])\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic White\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.6 (81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack/African American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.2 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmerican Indian/Alaska\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNative Hawaiian Other Pacific Islander\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeclined/Two or more/Other/Unknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.2 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePredominantly antibody deficiency type (% [n])\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplicated CVID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.0 (44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCommon variable immunodeficiency (CVID)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.1 (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary Hypogammaglobulinemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.4 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary Hypogammaglobulinemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.4 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecific antibody deficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.6 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgG subclass deficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.4 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eHRQoL in PAD patients\u003c/h2\u003e \u003cp\u003eWe compared the HRQoL in adult patients with primary PAD, stratified by disease severity. Our analysis compared core and individual HRQoL-14 questions across mild, moderate, and severe PAD patient groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Core HRQoL questions evaluated patients' perceptions of their overall health and the extent to which they experienced periods of suboptimal mental or physical health lasting more than two weeks.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of HRQoL-14 responses among mild, moderate, and severe PAD patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMild PAD\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModerate PAD\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSevere PAD\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eCore questions\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFair or poor self-rated health status (% [n])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.7 (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.7 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54.8 (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMental health not good for \u0026ge;\u0026thinsp;14 days (% [n])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.7 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.3 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.6 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical health not good for \u0026ge;\u0026thinsp;14 days (% [n])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.9 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.4 (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48.4 (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.81\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIndividual questions\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActivity limitation due to health problem\u003csup\u003ea\u003c/sup\u003e (% [n])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88.9 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92.0 (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71.0 (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeed for personal care assistance\u003csup\u003eb\u003c/sup\u003e (% [n])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.6 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.8 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.3 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeed for assistance with routine needs\u003csup\u003ec\u003c/sup\u003e (% [n])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.0 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.9 (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.7 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days during the past 30 days with poor physical health\u003csup\u003ed\u003c/sup\u003e (mean [std])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.4 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.1 (10.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.6 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days during the past 30 days with poor mental health\u003csup\u003ee\u003c/sup\u003e (mean [std])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.5 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.6 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.0 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days during the past 30 days that poor physical or mental health affected usual activities\u003csup\u003ef\u003c/sup\u003e (mean [std])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.7 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.4 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.0 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of months that activities limited by health problem (mean [std])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.0 (34.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111.5 (380.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52.2 (79.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days during the past 30 days that pain impacted usual activities (e.g., self-care, work, or recreation (mean [std])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.3 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.4 (9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.0 (10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days during the past 30 days felt depressed\u003csup\u003eg\u003c/sup\u003e (mean [std])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.3 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.5 (9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.8 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days during the past 30 days felt anxious or tense\u003csup\u003eh\u003c/sup\u003e (mean [std])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.9 (10.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.6 (10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.0 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days during the past 30 days lacked sufficient rest or sleep\u003csup\u003ei\u003c/sup\u003e (mean [std])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.9 (11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.2 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.4 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days during the past 30 days felt health and energetic\u003csup\u003ej\u003c/sup\u003e (mean [std])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1 (8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.5 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.0 (11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003eAre you LIMITED in any way in any activities because of any impairment or health problem?\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eb\u003c/sup\u003eBecause of any impairment or health problem, do you need the help of other persons with your PERSONAL CARE needs, such as eating, bathing, dressing, or getting around the house?\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ec\u003c/sup\u003eBecause of any impairment or health problem, do you need the help of other persons in handling your ROUTINE needs, such as everyday household chores, doing necessary business, shopping, or getting around for other purposes?\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ed\u003c/sup\u003eNow thinking about your physical health, which includes physical illness and injury, for how many days during the past 30 days was your physical health not good?\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ee\u003c/sup\u003eNow thinking about your mental health, which includes stress, depression, and problems with emotions, for how many days during the past 30 days was your mental health not good?\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ef\u003c/sup\u003eDuring the past 30 days, for about how many days did poor health keep you from doing your usual activities, such as self-care, work, or recreation?\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eg\u003c/sup\u003eDuring the past 30 days, for about how many days have you felt SAD, BLUE, or DEPRESSED?\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eh\u003c/sup\u003eDuring the past 30 days, for about how many days have you felt WORRIED, TENSE, or ANXIOUS?\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ei\u003c/sup\u003eDuring the past 30 days, for about how many days have you felt you did NOT get ENOUGH REST or SLEEP?\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ej\u003c/sup\u003eDuring the past 30 days, for about how many days have you felt VERY HEALTHY AND FULL OF ENERGY?\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe assessment of fair or poor self-rated health status revealed a gradient across disease severity groups. 66.7% of mild PAD patients (n\u0026thinsp;=\u0026thinsp;18) reported \u0026ldquo;fair or poor\u0026rdquo; health status, compared to 40.7% of those with moderate PAD (n\u0026thinsp;=\u0026thinsp;27), and 54.8% in the severe PAD group (n\u0026thinsp;=\u0026thinsp;31) (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Mental health challenges lasting for 14 or more days were reported by 16.7% of mild PAD patients, compared to 33.3% of patients with moderate PAD and 22.6% of those with severe PAD (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). The evaluation of physical health revealed that 38.9% of mild PAD patients (n\u0026thinsp;=\u0026thinsp;7) experienced poor physical health for 14 or more days, a slight increase to 44.4% for moderate PAD patients (n\u0026thinsp;=\u0026thinsp;12), and nearly half, 48.4%, for severe PAD patients (n\u0026thinsp;=\u0026thinsp;15), reported prolonged periods of poor physical health (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). There was no statistically significant difference across the disease severity groups.\u003c/p\u003e \u003cp\u003eThe impact of PAD on patients' daily activities was profound across all severity groups. The majority of patients reported limitations in activities due to health problems with 88.9% in the mild PAD group (n\u0026thinsp;=\u0026thinsp;16), 92.0% in the moderate PAD group (n\u0026thinsp;=\u0026thinsp;23), and 71.0% in the severe PAD group (n\u0026thinsp;=\u0026thinsp;22). Patients across all severity groups reported similar mean numbers of days with poor physical health (13.4 for mild vs. 13.1 for moderate vs. 13.6 for severe PAD) and mental health (5.5 for mild vs. 10.6 for moderate vs. 8.0 for severe PAD) within the past 30 days. The long-term impact on daily activities, as measured by the number of months that activities were limited by health issues, varied widely with patients with mild PAD reporting a mean of 32.0 months, patients with moderate PAD reporting a mean of 111.5 months, and patients with severe PAD reporting a mean of 52.2 months.\u003c/p\u003e \u003cp\u003ePain was reported as a key factor limiting usual activities for an average of 11.3, 9.4, and 9.0 days in the mild, moderate, and severe PAD groups, respectively. The percentage of patients needing assistance with personal care varied across severity groups, with 5.6% of mild PAD patients, 14.8% of moderate PAD patients, and 13.3% of severe PAD patients reporting this need. Assistance with routine needs was consistently reported by patients across severity levels, with 50.0% in the mild (n\u0026thinsp;=\u0026thinsp;9), 51.9% in the moderate (n\u0026thinsp;=\u0026thinsp;14), and 36.7% in the severe (n\u0026thinsp;=\u0026thinsp;11) groups.\u003c/p\u003e \u003cp\u003eEmotional well-being, measured by days felt sad or depressed, was variable between groups, with a slightly higher mean of 9.5 days in the moderate PAD group compared to 4.3 and 4.8 days in the mild and severe groups, respectively. Similarly, anxiety levels were similar across severity groups, with the average number of days feeling anxious being 8.9 for mild, 12.6 for moderate, and 7.0 for severe PAD. Sleep disturbances, measured by the number of days not feeling rested or having enough sleep, also showed no significant difference, with an average of 14.9 days for mild, 15.2 for moderate, and 11.4 for severe PAD patients.\u003c/p\u003e \u003cp\u003eWe compared the core HRQoL-14 questions between primary PAD patients (n\u0026thinsp;=\u0026thinsp;76) and secondary PAD patients (n\u0026thinsp;=\u0026thinsp;7). 55.2% of primary PAD patients reported \u0026ldquo;fair or poor\u0026rdquo; health status, compared to 28.5% of secondary PAD patients (p\u0026thinsp;=\u0026thinsp;0.18) (Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). In the mental health domain, 34.2% of primary PAD patients reported challenges lasting 14 or more days, whereas only 14.3% of secondary PAD patients reported similar challenges (p\u0026thinsp;=\u0026thinsp;0.28) (Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Physical health assessments revealed that 51.3% of primary PAD patients experienced poor physical health for 14 or more days, compared to 28.5% of secondary PAD patients (p\u0026thinsp;=\u0026thinsp;0.25) (Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e2\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003eAmong CVID patients, we compared the core HRQoL-14 responses between complicated (n\u0026thinsp;=\u0026thinsp;44) and uncomplicated (n\u0026thinsp;=\u0026thinsp;20) CVID patients. Patients with complicated CVID were more likely to rate their health as \"fair\" or \"poor\" (56.8%, n\u0026thinsp;=\u0026thinsp;25) compared to those with uncomplicated CVID (40%, n\u0026thinsp;=\u0026thinsp;8) (p\u0026thinsp;=\u0026thinsp;0.21) (Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). Mental health challenges lasting for 14 or more days were reported by 31.8% of patients with complicated CVID, compared to a slightly higher 40% of those with uncomplicated CVID (p\u0026thinsp;=\u0026thinsp;0.52) (Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). The evaluation of physical health revealed that 47.7% of patients with complicated CVID experienced poor physical health for 14 or more days, compared to a prolonged period reported by 55% of those with uncomplicated CVID (p\u0026thinsp;=\u0026thinsp;0.59) (Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e3\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003eAlthough trends in the data suggest a relationship between increased disease severity and poorer HRQoL\u0026mdash; especially in terms of physical health and fair or poor self-rated health status\u0026mdash;the differences did not reach statistical significance, likely due to sample size. Similarly, when we stratified the analyses by therapies received and genetic testing, no statistically significant differences were observed when comparing those with and without immunoglobulin replacement therapy (IgRT) (Supplemental Figure S1), having received immunomodulator therapy (Supplemental Figure S2), or having an identified genetic etiology (Supplemental Figures S3). This may imply that the diagnosis of PAD itself, irrespective of the severity level, imposes a substantial burden on the HRQoL of patients.\u003c/p\u003e \u003cp\u003eWe further evaluated the core HRQoL-14 responses between primary PAD patients with (n\u0026thinsp;=\u0026thinsp;41) and without (n\u0026thinsp;=\u0026thinsp;35) autoinflammatory features. In the mental health domain, 78% of patients with autoinflammatory features reported challenges lasting 14 or more days, significantly higher than the 54.3% of patients without these features (p\u0026thinsp;=\u0026thinsp;0.02) (Fig.\u0026nbsp;\u003cspan refid=\"Fig12\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). A similar trend was noted in the other two domains. Patients with autoinflammatory features were more likely to rate their health as \"fair\" or \"poor\" (61%) compared to those without autoinflammatory features (48.6%) (p\u0026thinsp;=\u0026thinsp;0.28) (Fig.\u0026nbsp;\u003cspan refid=\"Fig12\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). Physical health assessments indicated that 53.7% of patients with autoinflammatory features experienced poor physical health for 14 or more days, compared to 48.6% of those without (p\u0026thinsp;=\u0026thinsp;0.66) (Fig.\u0026nbsp;\u003cspan refid=\"Fig12\" class=\"InternalRef\"\u003e4\u003c/span\u003eC). However, these differences were not statistically significant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eHRQoL is lower in PAD patients compared to healthy controls\u003c/h2\u003e \u003cp\u003eWe conducted a comparative analysis of HRQoL-14 Healthy Days Measure questionnaire responses between PAD patients (n\u0026thinsp;=\u0026thinsp;83) and a control group of the general population (n\u0026thinsp;=\u0026thinsp;801,582) from CDC-BRFSS data from a similar geographic area (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Patients with PAD were more likely to evaluate their health as \u0026ldquo;fair\u0026rdquo; or \u0026ldquo;poor\u0026rdquo; (53%, n\u0026thinsp;=\u0026thinsp;44), which was significantly higher than the 12.0% in the CDC-BRFSS comparator group (n\u0026thinsp;=\u0026thinsp;96,190), indicating a marked impact of PAD on self-perceived health (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig13\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). In the mental health domain, 24.1% of PAD patients (n\u0026thinsp;=\u0026thinsp;20) reported challenges lasting 14 or more days, which was significantly more than the 14.7% in the CDC-BRFSS comparator group (n\u0026thinsp;=\u0026thinsp;117,833) (p\u0026thinsp;=\u0026thinsp;0.02) (Fig.\u0026nbsp;\u003cspan refid=\"Fig13\" class=\"InternalRef\"\u003e5\u003c/span\u003eB). Physical health assessments further illustrated the PAD patients' burden, with 44.6% (n\u0026thinsp;=\u0026thinsp;37) experiencing poor physical health for 14 or more days, notably higher than the 8.0% in the CDC-BRFSS comparator group (n\u0026thinsp;=\u0026thinsp;64,127) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig13\" class=\"InternalRef\"\u003e5\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of HRQoL-14 responses among PAD patients and BRFSS respondents.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026minus;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSample Size\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCases No.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eProportion (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFair or poor self-rated health status (% [n])\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e53.0% (42.3%-63.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCDC-BRFSS Controls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e801,582\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e96,190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e12.0% (10.7%-13.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMental health not good for \u0026ge;\u0026thinsp;14 days (% [n])\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e24.1% (14.9%-33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCDC-BRFSS Controls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e801,582\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e117,833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e14.7% (13.6%-15.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePhysical health not good for \u0026ge;\u0026thinsp;14 days (% [n])\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e44.6% (33.9%-55.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCDC-BRFSS Controls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e801,582\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64,127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e8.0% (7.3%-8.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn our study, we evaluated the HRQoL using the CDC HRQoL-14 Healthy Days Measure questionnaire among patients with mild, moderate, and severe primary PAD. Additionally, we compared HRQoL across several strata including primary and secondary PAD, complicated and uncomplicated CVID patients, presence and absence of autoinflammatory features, and between those receiving or not receiving immunoglobulin replacement and immunomodulator therapies. We also compared the HRQoL of PAD patients with that of the general population, utilizing data from the CDC-BRFSS. Consistent with prior research, we observed that PAD has a significant negative impact on patients' quality of life when compared to the general population.\u003c/p\u003e \u003cp\u003eOur assessment of HRQoL among PAD patients revealed that the burden of the disease on QoL was evident across all levels of disease severity. Our analysis did not reveal a direct correlation between increasing severity and lower HRQoL scores; instead, it revealed a more complex pattern. While a high percentage of mild PAD patients reported fair or poor self-rated health status, this did not linearly increase with disease severity. Despite nearly half of the severe PAD group reporting extended periods of poor physical health, this percentage was not significantly higher than that reported by the mild group. Activity limitations, another key indicator of HRQoL, were reported by a substantial majority of patients across all severity groups. Moreover, the need for assistance with personal care and routine needs, as well as emotional and sleep disturbances, showed no significant variation across the disease severity spectrum.\u003c/p\u003e \u003cp\u003eComparing primary and secondary PAD patients, we found that primary PAD patients reported worse HRQoL outcomes. A higher proportion of primary PAD patients rated their health as \"fair or poor\" and experienced prolonged periods of poor physical and mental health compared to secondary PAD patients.\u003c/p\u003e \u003cp\u003eNotably, primary PAD patients with autoinflammatory features exhibited significantly worse mental health outcomes, with 78% reporting challenges lasting 14 or more days, compared to 54.29% of those without autoinflammatory features. While trends in physical health and overall health ratings followed a similar pattern, these differences were not statistically significant, which may have been limited by sample size. Similarly, our extended analysis, including stratifications based on immunoglobulin replacement therapy, immunomodulator therapy, and identified genetic etiology, did not reveal statistically significant differences across the three domains. These findings suggest that the diagnosis of PAD itself, regardless of severity, places a substantial burden on patients' HRQoL. This indicates that factors beyond disease severity, such as psychosocial or environmental factors, psychological resilience, and coping mechanisms developed over time, may significantly influence quality of life. These factors could potentially buffer the impact of disease progression on perceived well-being, highlighting the need for comprehensive care approaches that address not only the physical but also the mental and social aspects of living with PAD.\u003c/p\u003e \u003cp\u003eThe comparison of HRQoL between PAD patients and the comparator population from the BRFSS data further highlights the significant impact of PAD on patients' lives. PAD patients were more than four times as likely to report fair or poor self-rated health compared to the CDC-BRFSS comparator group, a difference that was highly significant. PAD also had a substantial negative impact on mental health, with nearly a quarter reporting poor mental health for two weeks or more, a rate significantly higher than in the BRFSS data. Similarly, the physical domain was severely affected, with PAD patients experiencing poor physical health for extended periods at a rate more than five times higher than that of the general population. These findings highlight the need for targeted interventions in PAD patients, designed to mitigate the extensive impact of both mental and physical heath domains, and address the broad and complex needs that extend beyond the clinical diagnosis of PAD.\u003c/p\u003e \u003cp\u003eWhile treatments such as immunoglobulin replacement therapy (IgRT), antibiotic prophylaxis, and in severe cases, hematopoietic stem cell transplantation (HSCT), have notably improved survival rates for patients with PAD, patients still continue to face challenges in their physical and mental health. Therefore, assessing the HRQoL is critical for understanding the comprehensive impact of PAD on patients' daily lives and overall well-being. Of note, here we did not see QoL benefit from immunomodulator therapy. These data may suggest that additional or alternative targeted approaches are needed. Future work is needed to investigate these outcomes by specific immunomodulator therapy type, duration, and targeted treatment approach.\u003c/p\u003e \u003cp\u003eWhile several studies have investigated HRQoL in adults and pediatric patients with IEI, research has yet to focus on adult patients with PAD or to draw comparisons with healthy controls. Generally, data from these studies indicate that IEI patients have a significantly poorer overall health status and self-rated health when compared with those suffering from other chronic diseases.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Research reveals that IEI patients experience more severe mental health issues, such as depression, isolation, and anxiety, than those observed in the general population.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) These findings are consistent with previous research that has established psychosocial factors as substantial determinants of the incidence, QoL, and mortality rates associated with chronic illnesses.(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThere were several limitations to our study. Although we assessed a considerable number of PAD patients, the cohort was predominantly female and non-Hispanic White. Thus, the external validity of our findings might be limited, highlighting the need for future research involving PAD patients of more diverse backgrounds who are matched to healthy controls.(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e) Furthermore, the small sample size and the cross-sectional design of the study may restrict the generalizability of our findings and our ability to establish causality. The reliance on self-reported measures, while insightful for understanding patient experiences, could introduce response biases. Additionally, the recruitment of participants from a single center might not accurately represent the wider PAD patient population. Despite these limitations, our findings provide an essential foundation for future research aimed at enhancing the QoL for individuals with PAD. Further studies with larger, more diverse populations and longitudinal designs are needed to clarify the long-term impacts of PAD on HRQoL and validate the interventions that may improve outcomes for these patients.\u003c/p\u003e \u003cp\u003eIn conclusion, this study provides insights into the significant impact of PAD on HRQoL across all severity levels, demonstrating the necessity for care strategies that include mental and social health support alongside medical management. The findings also stress the importance of interventions tailored to all severity levels, not limited to those classified as a clinically severe phenotype. Though progress has been achieved in treating PAD, there is a heightened need to focus on improving patients' health-related quality of life. This requires creating strong methods for evaluating HRQoL and meeting the psychological and social needs of those with PAD. Future research, with a focus on long-term studies and a broader, more inclusive, demographic is needed to develop effective interventions that enhance quality of life for all patients with PAD.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePAD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epredominantly antibody deficiency\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHRQoL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehealth\u0026ndash;related quality of life\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCDC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecenters for disease control and prevention\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBRFSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebehavioral risk factor surveillance system\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIVIG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintravenous immunoglobulin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSCIG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esubcutaneous immunoglobulin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCVID\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecommon variable immunodeficiency\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSAD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003especific antibody deficiency\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIgG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eimmunoglobulin G\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIRB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einstitutional review board\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHSCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehematopoietic stem cell transplantation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIgRT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eimmunoglobulin replacement therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eANOVA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eanalysis of variance\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eS.B. study conception and design. A.E. and S.B. wrote the main manuscript text. B.Z. and A.E. analyzed the data and prepared the figures. J. S. H., M.T., and A.P. collected, extracted, cleaned, and analyzed the data. M.O., N.S., D.V.D and J.R.F. interpreted the results. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e \u003cstrong\u003eFunding/Support\u003c/strong\u003e \u003cp\u003eSara Barmettler is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number K23AI163350 and a faculty development award from the American Academy of Allergy Asthma \u0026amp; Immunology (AAAAI). Jocelyn R. Farmer was supported by a faculty development award from the American Academy of Allergy Asthma \u0026amp; Immunology (AAAAI) and the National Institute on Minority Health and Health Disparities of the National Institute of Health under award number R01MD017816. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDisclosure of Conflicts of Interest:\u003c/strong\u003e \u003cp\u003eJocelyn R. Farmer is an ongoing consultant for Pharming and has received investigator-initiated research grants from Pfizer, Bristol Myers Squibb, and Pharming with no direct relation to the work presented. Daniel DiGiacomo has received consulting fees from BASF.\u003c/p\u003e \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGathmann B, Grimbacher B, Beaute J, Dudoit Y, Mahlaoui N, Fischer A et al. The European internet-based patient and research database for primary immunodeficiencies: results 2006\u0026ndash;2008. Clin Exp Immunol. 2009;157(Suppl 1):3\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1365-2249.2009.03954.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1365-2249.2009.03954.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 19737289.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePicard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, et al. International union of immunological societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol. 2018;38:96\u0026ndash;128. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10875-017-0464-9\u003c/span\u003e\u003cspan address=\"10.1007/s10875-017-0464-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDurandy A, Kracker S, Fischer A. Primary antibody deficiencies. Nat Rev Immunol. 2013;13:519\u0026ndash;33. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/nri3466\u003c/span\u003e\u003cspan address=\"10.1038/nri3466\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLucas M, Lee M, Lortan J, Lopez-Granados E, Misbah S, Chapel H. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 2010;125:1354\u0026ndash;e601354. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jaci.2010.02.040\u003c/span\u003e\u003cspan address=\"10.1016/j.jaci.2010.02.040\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBousfiha A, Jeddane L, Picard C, Ailal F, Bobby Gaspar H, Al-Herz W, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2018;38:129\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10875-017-0465-8\u003c/span\u003e\u003cspan address=\"10.1007/s10875-017-0465-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186\u0026ndash;205. e1-78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheraghi T, Kalantari A, Shabestari MS, Abolhassani H, Eibel H, Hammarstr\u0026ouml;m L. Inborn Errors of Immunity. 1st ed. Academic; 2021. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/B978-0-12-821028-4.00006-3\u003c/span\u003e\u003cspan address=\"10.1016/B978-0-12-821028-4.00006-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBakas T, Mclennon SM, Carpenter JS, Buelow JM, Otte JL, Hanna KM, et al. Systematic review of health-related quality of life models. Health Qual Life outcomes. 2012;10:1\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/1477-7525-10-134\u003c/span\u003e\u003cspan address=\"10.1186/1477-7525-10-134\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMandzuk LL, McMillan DE. A concept analysis of quality of life. J Orthop Nurs. 2005;9:12\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.joon.2004.11.001\u003c/span\u003e\u003cspan address=\"10.1016/j.joon.2004.11.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeshko D, Kulbachinskaya E, Korsunskiy I, Kondrikova E, Pulvirenti F, Quinti I, et al. Health-related quality of life in children and adults with primary immunodeficiencies: a systematic review and meta-analysis. J Allergy Clin Immunology: Pract. 2019;7:1929\u0026ndash;e575. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jaip.2019.02.013\u003c/span\u003e\u003cspan address=\"10.1016/j.jaip.2019.02.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRavens-Sieberer U, Erhart M, Wille N, Wetzel R, Nickel J, Bullinger M. Generic health-related quality-of-life assessment in children and adolescents: methodological considerations. PharmacoEconomics. 2006;24:1199\u0026ndash;220. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2165/00019053-200624120-00005\u003c/span\u003e\u003cspan address=\"10.2165/00019053-200624120-00005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuburovic NB, Pasic S, Susic G, Stevanovic D, Kuburovic V, Zdravkovic S, et al. Health-related quality of life, anxiety, and depressive symptoms in children with primary immunodeficiencies. Patient Prefer Adherence. 2014;8:323\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2147/PPA.S58040\u003c/span\u003e\u003cspan address=\"10.2147/PPA.S58040\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 24672289. PMC: PMC3962398.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVarni JW, Burwinkle TM, Lane MM. Health-related quality of life measurement in pediatric clinical practice: an appraisal and precept for future research and application. Health Qual Life outcomes. 2005;3:1\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/1477-7525-3-34\u003c/span\u003e\u003cspan address=\"10.1186/1477-7525-3-34\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiao N, Huang X, Zang W, Kiselev S, Bolkov MA, Tuzankina IA, Chereshnev VA. Health-related quality of life in patients with inborn errors of immunity: a bibliometric analysis. Front Immunol. 2024;15:1371124. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2024.1371124\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2024.1371124\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJolles S, Orange JS, Gardulf A, Stein MR, Shapiro R, Borte M, Berger M. Current treatment options with immunoglobulin G for the individualization of care in patients with primary immunodeficiency disease. Clin Exp Immunol. 2015;179(2):146\u0026ndash;60. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/cei.12485\u003c/span\u003e\u003cspan address=\"10.1111/cei.12485\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 25384609; PMCID: PMC4298393.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTabolli S, Giannantoni P, Pulvirenti F, La Marra F, Granata G, Milito C, et al. Longitudinal study on health-related quality of life in a cohort of 96 patients with common variable immune deficiencies. Front Immunol. 2014;5:605. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2014.00605\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2014.00605\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoutes J, Costa-Carvalho BT, Grimbacher B, Paris K, Ochs HD, Filipovich A, et al. Health-related quality of life and health resource utilization in patients with primary immunodeficiency disease prior to and following 12 months of immunoglobulin G treatment. J Clin Immunol. 2016;36:450\u0026ndash;61. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10875-016-0279-0\u003c/span\u003e\u003cspan address=\"10.1007/s10875-016-0279-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNijhof LN, van Brussel M, Pots EM, van Litsenburg RR, van de Putte EM, van Montfrans JM, et al. Severe fatigue is common among pediatric patients with primary immunodeficiency and is not related to disease activity. J Clin Immunol. 2021;41:1198\u0026ndash;207. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10875-021-01013-7\u003c/span\u003e\u003cspan address=\"10.1007/s10875-021-01013-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManusama OR, van Beveren NJ, van Hagen PM, Drexhage HA, Dalm VA. Psychological symptoms in primary immunodeficiencies: a common comorbidity? J Clin Immunol. 2022;42:695-8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10875-022-01207-7\u003c/span\u003e\u003cspan address=\"10.1007/s10875-022-01207-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 35043302.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSowers KL, Gayda-Chelder CA, Galantino ML. Self-reported cognitive impairment in individuals with Primary Immunodeficiency Disease. Brain Behav Immunity-Health. 2020;9:100170. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.bbih.2020.100170\u003c/span\u003e\u003cspan address=\"10.1016/j.bbih.2020.100170\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRozanski A, Blumenthal JA, Davidson KW, Saab PG, Kubzansky L. The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. J Am Coll Cardiol. 2005;45:637\u0026ndash;51. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jacc.2004.12.005\u003c/span\u003e\u003cspan address=\"10.1016/j.jacc.2004.12.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuls J, Bunde J. Anger, anxiety, and depression as risk factors for cardiovascular disease: the problems and implications of overlapping affective dispositions. psychol Bull. 2005;131:260. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1037/0033-2909.131.2.260\u003c/span\u003e\u003cspan address=\"10.1037/0033-2909.131.2.260\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCallum SM, Batterham PJ, Calear AL, Sunderland M, Carragher N, Kazan D. Associations of fatigue and sleep disturbance with nine common mental disorders. J Psychosom Res. 2019;123:109727. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jpsychores.2019.05.005\u003c/span\u003e\u003cspan address=\"10.1016/j.jpsychores.2019.05.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCenters for Disease Control and Prevention Measuring Healthy Days. Population assessment of health-related quality of life. Atlanta Ga CDC Apr. 2024. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://archive.cdc.gov/#/details?url=https://www.cdc.gov/hrqol/index.htm\u003c/span\u003e\u003cspan address=\"https://archive.cdc.gov/#/details?url=https://www.cdc.gov/hrqol/index.htm\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePickens CM, Pierannunzi C, Garvin W, Town M. Surveillance for Certain Health Behaviors and Conditions Among States and Selected Local Areas - Behavioral Risk Factor Surveillance System, United States, 2015. MMWR Surveill Summ. 2018;67(9):1\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIachan R, Pierannunzi C, Healey K, Greenlund KJ, Town M. National weighting of data from the Behavioral Risk Factor Surveillance System (BRFSS). BMC Med Res Methodol. 2016;16(1):155.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. International Consensus Document (ICON): Common Variable Immunodeficiency Disorders. J Allergy Clin Immunol Pract. 2016;4(1):38\u0026ndash;59.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, et al. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol. 2020;40(1):66\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTandon M, DiGiacomo DV, Zhou B, Hesterberg P, Rosenberg CE, Barmettler S, Farmer JR. Response to SARS-CoV-2 initial series and additional dose vaccine in pediatric patients with predominantly antibody deficiency. Front Immunol. 2023;14:1217718. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2023.1217718\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2023.1217718\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 37575247; PMCID: PMC10413262.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang AM, Elmoursi A, DiGiacomo DV, Zhou B, Tandon M, Hong JS, Yang NJ, Ong MS, Dighe AS, Berrios C, Poznansky MC, Iafrate AJ, Naranbhai V, Balazs A, Pillai S, Farmer JR, Barmettler S. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response in adults with predominantly antibody deficiency. J Allergy Clin Immunol Glob. 2024;3(2):100234. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jacig.2024.100234\u003c/span\u003e\u003cspan address=\"10.1016/j.jacig.2024.100234\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 38544577; PMCID: PMC10965812.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSantos T, de Matos MG, Sim\u0026otilde;es C, Leal I. do C\u0026eacute;u MaChado M. (Health-related) quality of life and psychosocial factors in adolescents with chronic disease: A systematic literature review. Int J Adolesc Med Health. 2017;31:20170037. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1515/ijamh-2017-0037\u003c/span\u003e\u003cspan address=\"10.1515/ijamh-2017-0037\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSahle BW, Chen W, Melaku YA, Akombi BJ, Rawal LB, Renzaho AM. Association of psychosocial factors with risk of chronic diseases: A nationwide longitudinal study. Am J Prev Med. 2020;58:e39\u0026ndash;50. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.amepre.2019.09.007\u003c/span\u003e\u003cspan address=\"10.1016/j.amepre.2019.09.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHayes DK, Greenlund KJ, Denny CH, Neyer JR, Croft JB, Keenan NL. Racial/ethnic and socioeconomic disparities in health-related quality of life among people with coronary heart disease, 2007. Prev Chronic Dis. 2011;8(4):A78. Epub 2011 Jun 15. PMID: 21672402; PMCID: PMC3136984.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWallander JL, Fradkin C, Elliott MN, Tortolero S, Cuccaro P, Schuster MA. Racial/ethnic disparities in health-related quality of life and health status across pre-, early-, and mid-adolescence: a prospective cohort study. \u003cem\u003eQual Life Res\u003c/em\u003e. 2019;28:1761\u0026ndash;1771. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11136-019-02157-1\u003c/span\u003e\u003cspan address=\"10.1007/s11136-019-02157-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 30788576.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-clinical-immunology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joci","sideBox":"Learn more about [Journal of Clinical Immunology](https://www.springer.com/journal/10875)","snPcode":"10875","submissionUrl":"https://submission.nature.com/new-submission/10875/3","title":"Journal of Clinical Immunology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Predominantly antibody deficiency, Health-related quality of life , CDC HRQoL-14, Behavioral risk factor surveillance system, Immunodeficiency, Common variable immunodeficiency, Hypogammaglobulinemia, Immunoglobulin therapy, Chronic disease management, Mental health, Physical health, Patient-reported outcomes, ","lastPublishedDoi":"10.21203/rs.3.rs-4612913/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4612913/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHealth-related quality of life (HRQoL) measures individual well-being across physical, psychological, and social domains. Patients with predominantly antibody deficiency (PAD) are at risk for morbidity and mortality, however, the effect of these complications on HRQoL requires additional study. Patients with PAD were asked to voluntarily complete the Centers for Disease Control (CDC) HRQoL-14 Healthy Days Measure questionnaire. These results were compared to data from the CDC-initiated Behavioral Risk Factor Surveillance System (BRFSS), a cross-sectional questionnaire including questions from CDC-HRQOL-14. Statistical analyses included two-proportion Z-test, t-tests, and analysis of variance. 83 patients with PAD completed the survey. Patients were sub-stratified into mild (23.7%), moderate (35.5%), severe (40.8%), and secondary (8.4%) PAD. \"Fair or poor\" health status was reported in 52.6% of PAD patients. Mental health challenges\u0026thinsp;\u0026ge;\u0026thinsp;14 days/month occurred in 25% of patients. Physical health issues\u0026thinsp;\u0026ge;\u0026thinsp;14 days/month was reported in 44.7% of patients. Activity limitations were noted by 80.3% of patients. There were no statistically significant differences by PAD severity. Patients with autoinflammatory disease co-morbidities reported more mental health challenges compared to those without (78% vs. 54.3%, p\u0026thinsp;=\u0026thinsp;0.02). Compared to the CDC-BRFSS data, significantly more patients with PAD reported \"fair or poor\" health status (53% vs 12.0%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), mental health challenges (24.1% vs 14.7%; p\u0026thinsp;=\u0026thinsp;0.02), and poor physical health (44.6% vs 8.0%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Patients with PAD had significantly reduced HRQoL compared to CDC-BRFSS respondents from a similar geographical region. Decreased HRQoL was prevalent across all PAD severity levels. Additional research is needed to improve HRQoL for patients with PAD.\u003c/p\u003e","manuscriptTitle":"A Cross-Sectional Study of Health-Related Quality of Life in Patients with Predominantly Antibody Deficiency ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-18 20:26:31","doi":"10.21203/rs.3.rs-4612913/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-07T12:34:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-06T18:00:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"258019839336314940739434020000826633930","date":"2024-07-01T05:38:08+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-30T09:00:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-21T06:50:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-21T06:50:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Clinical Immunology","date":"2024-06-20T15:48:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-clinical-immunology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joci","sideBox":"Learn more about [Journal of Clinical Immunology](https://www.springer.com/journal/10875)","snPcode":"10875","submissionUrl":"https://submission.nature.com/new-submission/10875/3","title":"Journal of Clinical Immunology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"370b7701-2b0b-4906-a0b7-bf9fffa7d205","owner":[],"postedDate":"July 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-12T16:06:06+00:00","versionOfRecord":{"articleIdentity":"rs-4612913","link":"https://doi.org/10.1007/s10875-024-01781-y","journal":{"identity":"journal-of-clinical-immunology","isVorOnly":false,"title":"Journal of Clinical Immunology"},"publishedOn":"2024-08-07 15:58:05","publishedOnDateReadable":"August 7th, 2024"},"versionCreatedAt":"2024-07-18 20:26:31","video":"","vorDoi":"10.1007/s10875-024-01781-y","vorDoiUrl":"https://doi.org/10.1007/s10875-024-01781-y","workflowStages":[]},"version":"v1","identity":"rs-4612913","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4612913","identity":"rs-4612913","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}