Respiratory infectious burden in a cohort of antibody deficiency patients treated with immunoglobulin replacement therapy: The impact of lung pathology and gastroesophageal reflux disease

Abstract

Background: Antibody deficiencies result from reduced immunoglobulin levels and function, increasing susceptibility to, primarily, bacterial infection. Primary antibody deficiencies comprise intrinsic defects in B-cell physiology, often due to inherited errors. Hematological malignancies or B-cell suppressive therapy are major causes of secondary antibody deficiency. Although immunoglobulin replacement therapy (IGRT) reduces infectious burden in antibody deficiency patients, respiratory tract infections remain a significant health burden. We hypothesize that lung pathology and gastroesophageal reflux disease (GORD) increase the risk of pneumonia in antibody deficiency patients, as in the general population.

Objective: For our cohort of patients with primary antibody deficiency and secondary antibody deficiency, we reviewed their respiratory infectious burden and the impact of lung pathologies and GORD.

Methods: The medical records of 231 patients on IGRT at a tertiary referral center, from October 26, 2014, to February 19, 2021, were reviewed to determine microbial isolates from sputum samples and prevalence of common lung pathologies and GORD.

Results: Haemophilus and Pseudomonas species represent a large infectious burden, being identified in 30.2% and 21.4% of sputum samples demonstrating growth, respectively; filamentous fungal and mycobacterial infections were rare. Diagnosed lung pathology increased the proportion of patients with Pseudomonas, Klebsiella, Stenotrophomonas, and Candida species isolated in their sputum, and diagnosed GORD increased the proportion with Enterobacter and Candida species isolated.

Conclusions: Bacterial respiratory infectious burden remains in primary antibody deficiency and secondary antibody deficiency despite IGRT. Lung pathologies encourage growth of species less susceptible to IGRT, so specialist respiratory medicine input and additional treatments such as inhaled antibiotics are indicated to optimize respiratory outcomes.

Keywords: Antibody deficiency; gastroesophageal reflux disease; immunoglobulin replacement therapy; lung pathology; microbiology; sputum cultures.

Fig 1

As anticipated, Fig 1 shows that the presence of lung pathology has a significant impact on microbial isolates from patients’ sputum samples. In particular, those with lung pathology were more likely to grow Candida species, Stenotrophomonas maltophilia, and Pseudomonas and Klebsiella species in their sputa. The proportion of patients growing these bacteria rose from 6.6% to 28.2%, from 0.8% to 10.0%, from 9.9% to 24.5%, and from 2.5% to 9.1%, respectively (P < .001, .003, .003, and .029). Meanwhile the proportion of patients growing Mycobacterium species and the commonly observed Haemophilus species was relatively unaffected.

Fig 2

Fig 2 shows that when GORD is present, the infectious profile is altered, with the proportion of patients growing Candida species in their sputum samples increasing from 14.8% to 38.1% (P < .01; odds ratio = 3.55) and the proportion of those growing Enterobacter species increasing from 1.9% to 19.0% (P < .001; odds ratio = 12.12). Other species such as Pseudomonas species and Klebsiella species were also seen more frequently in patients with GORD; however, these changes were not statistically significant. A further breakdown of the above results is provided by Table E3 (in the Online Repository available at www.jaci-global.org).