Primary antibody deficiencies (PAD) are the most frequently diagnosed primary immunodeficiencies and predispose to infections as well as numerous long-term sequelae. Study of PAD has largely been limited to tertiary referral centers that might over-represent ethnic and socioeconomic groups with fewer impediments to health care.1 As well-financed hospitals are more likely to achieve high quality care, under-resourced medical centers may face distinct challenges in managing complex disorders like PAD.2 While awareness of barriers to health care has increased, little is known regarding potential disparities in PAD diagnosis and management.
Boston Medical Center (BMC) is the largest safety-net hospital (legally obligated to provide healthcare for individuals regardless of their insurance status) in New England. More than two-thirds of BMC patients receive government-sponsored health insurance or are uninsured, more than 50% have income below the federal poverty level, and about one-third do not speak English as a primary language. In 2019, about half of BMC outpatients identified as Black/African-American (49.85%) and 16.74% identified as Hispanic/Latinx (see Table E1 in the online repository). Patients with PAD at BMC have not been previously studied.
Electronic medical records at BMC were reviewed retrospectively from January 2012 until January 2019 containing these PAD diagnoses: common variable immunodeficiency (CVID) (ICD-10 D83, D83.0, D83.1, D83.2, D83.8, D83.9, ICD-9 279.06), hereditary hypogammaglobulinemia (ICD-10 D80.0, ICD-9 279.04), nonfamilial hypogammaglobulinemia (ICD-10 D80.1, ICD-9 279.01), and IgG deficiency (ICD-10 D80.3, ICD-9 279.03). Diagnosis of CVID was defined by low IgG and IgA and/or IgM (IgG ≤ 600 mg/dL, IgA< 45 mg/dL, IgM < 35 mg/dL), poor response to vaccines, and exclusion of other causes of hypogammaglobulinemia. Diagnosis of hypogammaglobulinemia was defined by IgG < 600 mg/dL, but normal IgA and IgM, without secondary cause. This study was approved by the Institutional Review Board of Boston University.
Eighty-three patients with confirmed PAD were identified from review of BMC records, with 9.6% identifying as Black/African-American and 10.8% identifying as Hispanic/Latinx. While notably lower than the respective percentages of total BMC outpatients, the proportions of PAD patients identifying as Black/African-American or Hispanic/Latinx were significantly higher than that of the United States Immunodeficiency Network (USIDNET) registry (Table E2). While future efforts are necessary to explain demographic differences among total outpatients and PAD at BMC, there are clear demographic differences between the BMC and USIDNET cohorts.
We next examined whether management of PAD differed between BMC and USIDNET. Immunoglobulin replacement therapy (IRT) is vital for many with PAD, reducing the frequency of severe infections.3 IRT was far less frequently prescribed to those at BMC with PAD compared to USIDNET PAD patients (30.1% vs 86.8%, P < 0.0001, Table I), including a profound difference in those with hypogammaglobluinemia (17% vs 66.5%, P < 0.0001). The reduced usage of IRT did coincide with higher median diagnostic IgG values at BMC. However, discrepancy of treatment persisted in those with severe PAD for which IRT is typically provided,4 with reduced usage of IRT at BMC for CVID (60.9% vs 88.6%, P < 0.0001) and those with IgG < 500 (39.3% vs 94.1%, P < 0.0001). We found no difference in the proportion of PAD patients receiving IRT in the USIDNET cohort on the basis of sex (86.7% of females receiving IRT vs. 86.1% of males, P = 0.774), but in the BMC cohort there appeared to be a trend towards reduced IRT in males (36.8% of females vs 18.2% of males, P = 0.0703). Together these data raise concern of disparity in IRT usage for those with severe PAD at BMC.
Table I.
PAD patients receiving immunoglobulin replacement therapy (IRT).
| Diagnosis | BMC | USIDNET | P value |
|---|---|---|---|
| Total PAD | 83 | 2502 | |
| PAD subjects on IRT | 25 (30.1%) | 2172 (86.8%) | < 0.0001 |
| Median IgG mg/dL (95% CI) | 480.5 (432 – 499) | 323 (303 – 345) | < 0.0001 |
| Total hypogammaglobulinemia | 47 | 212 | |
| Hypogammaglobulinemia on IRT | 8 (17.0%) | 141 (66.5%) | < 0.0001 |
| Median IgG mg/dL (95% CI) | 500 (463 – 534) | 442.5 (375 – 503) | 0.034 |
| Total CVID | 23 | 1814 | |
| CVID on IRT | 14 (60.9%) | 1608 (88.6%) | < 0.0001 |
| Median IgG mg/dL (95% CI) | 449 (346 – 490) | 351 (324 – 371) | 0.061 |
| Total IgG < 500 mg/dL | 28 | 573 | |
| IgG < 500 mg/dL on IRT | 11 (39.3%) | 539 (94.1%) | < 0.0001 |
| Median IgG mg/dL (95% CI) | 433.5 (396 – 476) | 444.5 (432 – 450) | 0.539 |
BMC, Boston Medical Center; CVID, common variable immunodeficiency; IRT, immunoglobulin replacement therapy; PAD, primary antibody deficiency; USIDNET, United States Immnodeficiency Network. P value calculated by Chi-square test.
Inadequate usage of IRT may increase pulmonary complications of PAD or indicate subpar clinical management that leads to chronic lung disease.5 Pneumonia occurred significantly more often in those identifying as Black/African-American (75%) compared to all others in the BMC PAD cohort (33%, P = 0.04, Table II). The pneumonia rate of 75% we found in African-American subjects in the BMC PAD cohort is much higher than a single center study from New York where 39.5% of hypogammaglobulinemia patients and 42.2% of CVID patients had pneumonia.6 Bronchiectasis is an obstructive pulmonary disease in which dilation of the bronchi results from increased susceptibility to infection and inflammatory dysregulation of PAD.7 Bronchiectasis occurred more frequently in Black/African-American patients (75%) compared to other BMC PAD patients (11%, P = 0.0002). Additionally, a greater proportion of PAD patients residing in the Massachusetts county of Suffolk (35%), which includes the city of Boston and has a median household income of $64,582, had bronchiectasis compared to the neighboring counties of Middlesex and Norfolk, with median house incomes of $97,012 and $99,511, respectively (4.5%, P = 0.02) (incomes from census.gov). The rates of bronchiectasis we observed in Black and Suffolk patients from the BMC PAD cohort were markedly higher than USIDNET patients with CVID (13.5%), X-linked agammaglobulinemia (8.4%), or hypogammaglobulinemia (6.5%).6, 8 We found no demographic differences for asthma, chronic obstructive pulmonary disease, or interstitial lung disease within our cohort. Potentially contributing to differences in outcome, there were 30 different providers for 72 PAD patients (2.4 patients/provider) at BMC, and 11 patients had no provider managing their PAD. In contrast, the USIDNET cohort consisted of physicians with greater specialized care of PAD as there were 20.7 patients per provider.
Table II.
Pulmonary complications by ethnicity, ethnicity, and county in the BMC PAD cohort.
| Total | Black/African- American |
All others | P value | Hispanic/Latinx | All others | P value | Suffolk County |
Middlesex and Norfolk Counties |
P value | |
|---|---|---|---|---|---|---|---|---|---|---|
| Subjects | 83 | 8 | 75 | 9 | 74 | 23 | 22 | |||
| Complications | ||||||||||
| Pneumonia | 31 (37%) | 6 (75%) | 25 (33%) | 0.04 | 4 (44%) | 27 (37%) | 0.72 | 12 (52%) | 7 (32%) | 0.23 |
| Asthma | 14 (17%) | 3 (38%) | 11 (15%) | 0.13 | 3 (33%) | 11 (15%) | 0.17 | 5 (22%) | 4 (18%) | >0.9999 |
| Bronchiectasis | 14 (17%) | 6 (75%) | 8 (11%) | 0.0002 | 2 (22%) | 12 (16%) | 0.64 | 8 (35%) | 1 (4.5%) | 0.02 |
| COPD | 17 (21%) | 0 (0%) | 17 (23%) | 0.20 | 1 (11%) | 16 (22%) | 0.68 | 7 (30%) | 2 (9%) | 0.14 |
| Interstitial lung disease | 10 (12%) | 1 (13%) | 9 (12%) | 0.59 | 0 (0%) | 10 (14%) | 0.59 | 1 (4.4%) | 4 (18%) | 0.19 |
BMC, Boston Medical Center; COPD, chronic obstructive pulmonary disease; PAD, primary antibody deficiency. P value calculated by Fisher’s exact test.
Our report presents the first description of clinical disparity of PAD patients at a safety net hospital. Global analysis has provided evidence that CVID diagnosis occurs less often in developing countries, indicating that socioeconomic factors may limit identification of PAD.9 Though a limited single center study of a small PAD cohort, our data demonstrates reduced IRT usage and increased bronchiectasis prevalence at a safety net hospital, particularly among those identifying as Black or from an urban county with lower median income. As this is a preliminary observation, additional research is necessary to conclusively demonstrate clinical disparity of immunodeficient patients and explore ways to resolve such issues. Our results highlight the potential importance of specialized care of PAD by immunologists and incorporation of diverse medical centers into studies of PAD.
Supplementary Material
Clinical Implications.
Little is known regarding how socioeconomic factors influence diagnosis and care of primary antibody deficiencies. In our single center study of an urban safety net hospital, we found disparity of treatment and clinical course of patients with primary antibody deficiencies.
Acknowledgements
We thank Linda Rosen, research manager at the Clinical Data Warehouse of the Boston University School of Medicine, for assistance with our research query as well as all physicians who enrolled patients to USIDNET.
This work was funded by National Institutes of Health grants AI137183, AI151486, HL139444, and an AAAAI Foundation Faculty Development Award. The funding sources were not involved in the collection, analysis, interpretation of data, preparation of the manuscript, or decision to submit this report for publication.
Footnotes
The authors declare no conflicts of interest.
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