Screening for Humoral Immunodeficiency in Patients with Community-Acquired Pneumonia
BACKGROUND: Immunodeficiency is an underrecognized risk factor for infections, such as community-acquired pneumonia (CAP).
OBJECTIVE: We evaluated patients admitted with CAP for humoral immunodeficiency.
DESIGN: Prospective cohort study.
SETTING: Inpatients
PATIENTS, INTERVENTION, AND MEASUREMENTS: We enrolled 100 consecutive patients admitted with a diagnosis of CAP from February 2017 to April 2017. Serum IgG, IgM, IgA, and IgE levels were obtained within the first 24 hours of admission. CURB-65 score and length of hospital stay were calculated. The Wilcoxon rank-sum test, Kruskal-Wallis test, and simple linear regression analysis were used in data analysis.
RESULTS: The prevalence of hypogammaglobinemia in patients with CAP was 38% (95% CI: 28.47% to 48.25%). Twenty-seven of 100 patients had IgG hypogammaglobinemia (median: 598 mg/dL, IQ range: 459-654), 23 of 100 had IgM hypogammaglobinemia (median: 38 mg/dL, IQ range: 25-43), and 6 of 100 had IgA hypogammaglobinemia (median: 36 mg/dL, IQ range: 18-50). The median hospital length of stay for patients with IgG hypogammaglobinemia was significantly higher when compared to patients with normal IgG levels (five days, IQ range [3-10] vs three days, IQ range [2-5], P = .0085). Fourteen patients underwent further immune evaluation, resulting in one diagnosis of multiple myeloma, three patients diagnosed with specific antibody deficiency, and one patient diagnosed with selective IgA deficiency.
CONCLUSION: There is a high prevalence of hypogammaglobinemia in patients hospitalized with CAP, with IgG and IgM being the most commonly affected classes. IgG hypogammaglobinemia was associated with an increased length of hospitalization. Screening immunoglobulin levels in CAP patients may also uncover underlying humoral immunodeficiency or immuno-proliferative disorders.
© 2018 Society of Hospital Medicine
METHODS
Study Design
This was a prospective cohort study conducted at Rochester General Hospital, a 528-bed tertiary care medical center, from February 2017 to April 2017. We enrolled 100 consecutive patients admitted to the inpatient internal medicine service with a physician diagnosis of CAP. Written consent was obtained from each patient. The study was approved by the institutional review board at Rochester General Hospital.
Case Definition
The following criteria were used to diagnose CAP: (1) Respiratory symptoms of productive cough or pleuritic chest pain, (2) Fever >38°C before or at the time of admission, and (3) chest imaging with infiltrate. Exclusion criteria included a diagnosis of hospital-acquired pneumonia, prior diagnosis of primary immunodeficiency, immunosuppression due to an underlying condition, such as HIV or malignancy, therapy with immunosuppressive medications including chemotherapy, Ig replacement within the past six months, or treatment with >10 mg prednisone for greater than 14 days before hospital admission.
Patients underwent an additional evaluation by a clinical immunologist if they met one of the following criteria: any hypergammaglobinemia (elevated IgG, IgM, or IgA), IgG hypogammaglobinemia <550 mg/dL, undetectable IgM or IgA, or if IgG, IgM, and IgA were all below the lower limit of normal.
CURB-65 was used for estimation of the severity of illness with CAP. The components of the score include age ≥65, confusion, BUN >19 mg/dl, respiratory rate ≥30 breaths per minute and systolic blood pressure <90 mm Hg or diastolic blood pressure ≤60 mm Hg. Each component is scored zero if absent or one if present. Predicted mortality ranges from 0.6% for a score of zero to 27.8% for a score of 5.
Data Collection
Patient health information including age, race, gender, medical history, admission notes, results of chest imaging studies, and relevant laboratory studies including serum levels of IgG, IgM, IgA, IgE on admission was obtained from the electronic medical health record. An additional evaluation by the immunologist occurred within three months of hospital discharge and included repeat Ig levels, pre- and postvaccination titers of polysaccharide and peptide antigens, serum protein electrophoresis, and B & T cell panels.
Description of Normal Levels
The normal levels of immunoglobulins were defined based on standard reference ranges at the laboratory at Rochester General Hospital; IgG (700-1,600 mg/dl), IgM (50-300 mg/dl), IgA (70-400 mg/dl), and IgE (0-378 IU/ml). Although there is no established classification regarding the degree of IgG hypogammaglobinemia,16 clinical immunologists commonly classify the severity of IgG hypogammaglobinemia as follows: mild (550-699 mg/dL), moderate (400-549 mg/dL), and severe (<400 mg/dL) IgG hypogammaglobinemia.
Statistical Analysis
Statistical analysis was performed using STATA software (StataCorp LLC, College Station, Texas). We conducted a Wilcoxon rank-sum test to compare the median difference in length of stay between groups with a low versus normal range of immunoglobulins. A Kruskal–Wallis test was performed to check for the median difference in IgG levels across degrees of illness severity (CURB-65 score categories). We conducted a simple linear regression analysis using the logarithmic data of the length of stay and IgG level variables. A chi-square test was used to determine the association between comorbidities and Ig levels.
