Skip to main content
Top
Published in: Journal of Clinical Immunology 7/2022

02-07-2022 | Bronchiectasis | Original Article

Risk Factors of Pneumonia in Primary Antibody Deficiency Patients Receiving Immunoglobulin Therapy: Data from the US Immunodeficiency Network (USIDNET)

Authors: Maha N. Syed, Carleigh Kutac, Jennifer M. Miller, Rebecca Marsh, Kathleen E. Sullivan, Charlotte Cunningham-Rundles, Ramsay L. Fuleihan, Farrah Kheradmand, Joud Hajjar

Published in: Journal of Clinical Immunology | Issue 7/2022

Login to get access

Abstract

Background

Despite immunoglobulin replacement (IgRT) therapy, some patients with primary antibody deficiency (PAD) continue to develop respiratory infections. Recurrent and severe respiratory infections, particularly pneumonia, can lead to significant morbidity and mortality. Therefore, we sought to determine the risk factors of developing pneumonia in PAD patients, already receiving IgRT.

Methods

We evaluated clinical and laboratory features of PAD patients enrolled in the US Immune Deficiency Network (USIDNET) registry by April 2017. Patients were included if they met the following criteria: (1) PAD diagnosis (common variable immunodeficiency (CVID), agammaglobulinemia, hypogammaglobinemia, and specific antibody deficiency (SAD) and (2) available data on infections before and after IgRT. Patients were excluded if they were not receiving IgRT, or if no pre/post infections data were available. Descriptive and multivariable logistic regression analyses were used to identify factors associated with pneumonia post-IgRT.

Results

A total of 1232 patients met the inclusion criteria. Following IgRT, 218 patients (17.7%) were reported to have at least one pneumonia episode. Using multivariate logistic regression analysis, we found a statistically significant increased risk of pneumonia in patients with asthma (OR: 2.55, 95% CI (1.69–3.85), p < 0.001) bronchiectasis (OR: 3.94, 95% CI (2.29–6.80), p < 0.001), interstitial lung disease (ILD) (OR: 3.28, 95%CI (1.43–7.56), p < 0.005), splenomegaly (OR: 2.02, 95%CI (1.08–3.76), p < 0.027), allergies (OR: 2.44, 95% CI [1.44–4.13], p = 0.001), and patients who were not on immunosuppressives (OR: 1.61; 95%CI [1.06–2.46]; p = 0.027). For every 50 unit increase in IgA, the odds of reporting pneumonia post IgRT decreased (OR: 0.86, 95% CI [0.73–1.02], p = 0.062).
Infectious organisms were reported in 35 of 218 patients who reported pneumonia after IgRT. Haemophilus influenzae was the most frequently reported (n = 11, 31.43%), followed by Streptococcus pneumoniae (n = 7, 20.00%).

Conclusion

Our findings suggest PAD patients with chronic and structural lung disease, splenomegaly, and allergies were associated with persistent pneumonia. However, our study is limited by the cross-sectional nature of the USIDNET database and limited longitudinal data. Further studies are warranted to identify susceptible causes and explore targeted solutions for prevention and associated morbidity and mortality.

Clinical Implications

Patients with primary antibody deficiency with structural lung disease, allergies, and splenomegaly are associated with persistent pneumonia post-IgRT.
Appendix
Available only for authorised users
Literature
1.
go back to reference Wood P. Primary antibody deficiencies: recognition, clinical diagnosis and referral of patients. Clin Med (Lond). 2009;9:595–9.CrossRef Wood P. Primary antibody deficiencies: recognition, clinical diagnosis and referral of patients. Clin Med (Lond). 2009;9:595–9.CrossRef
2.
go back to reference Hampson F, Chandra A, Screaton N, Condliffe A, Kumararatne D, Exley A, et al. Respiratory disease in common variable immunodeficiency and other primary immunodeficiency disorders. Clin Radiol. 2012;67:587–95.CrossRefPubMed Hampson F, Chandra A, Screaton N, Condliffe A, Kumararatne D, Exley A, et al. Respiratory disease in common variable immunodeficiency and other primary immunodeficiency disorders. Clin Radiol. 2012;67:587–95.CrossRefPubMed
3.
go back to reference Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48.CrossRefPubMed Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48.CrossRefPubMed
4.
go back to reference Jiang F, Torgerson TR, Ayars AG. Health-related quality of life in patients with primary immunodeficiency disease. Allergy Asthma Clin Immunol. 2015;11:27.CrossRefPubMedPubMedCentral Jiang F, Torgerson TR, Ayars AG. Health-related quality of life in patients with primary immunodeficiency disease. Allergy Asthma Clin Immunol. 2015;11:27.CrossRefPubMedPubMedCentral
5.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
6.
go back to reference Good RA, Mazzitello WF. Chest disease in patients with agammaglobulinemia. Dis Chest. 1956;29:9–35.CrossRefPubMed Good RA, Mazzitello WF. Chest disease in patients with agammaglobulinemia. Dis Chest. 1956;29:9–35.CrossRefPubMed
7.
go back to reference Pasteur MC, Bilton D, Hill AT, British Thoracic Society Bronchiectasis non CFGG. British Thoracic Society guideline for non-CF bronchiectasis. Thorax 2010; 65 Suppl 1:i1–58. Pasteur MC, Bilton D, Hill AT, British Thoracic Society Bronchiectasis non CFGG. British Thoracic Society guideline for non-CF bronchiectasis. Thorax 2010; 65 Suppl 1:i1–58.
8.
go back to reference Sweinberg SK, Wodell RA, Grodofsky MP, Greene JM, Conley ME. Retrospective analysis of the incidence of pulmonary disease in hypogammaglobulinemia. J Allergy Clin Immunol. 1991;88:96–104.CrossRefPubMed Sweinberg SK, Wodell RA, Grodofsky MP, Greene JM, Conley ME. Retrospective analysis of the incidence of pulmonary disease in hypogammaglobulinemia. J Allergy Clin Immunol. 1991;88:96–104.CrossRefPubMed
9.
go back to reference Tarzi MD, Grigoriadou S, Carr SB, Kuitert LM, Longhurst HJ. Clinical immunology review series: an approach to the management of pulmonary disease in primary antibody deficiency. Clin Exp Immunol. 2009;155:147–55.CrossRefPubMedPubMedCentral Tarzi MD, Grigoriadou S, Carr SB, Kuitert LM, Longhurst HJ. Clinical immunology review series: an approach to the management of pulmonary disease in primary antibody deficiency. Clin Exp Immunol. 2009;155:147–55.CrossRefPubMedPubMedCentral
10.
go back to reference Kainulainen L, Varpula M, Liippo K, Svedstrom E, Nikoskelainen J, Ruuskanen O. Pulmonary abnormalities in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol. 1999;104:1031–6.CrossRefPubMed Kainulainen L, Varpula M, Liippo K, Svedstrom E, Nikoskelainen J, Ruuskanen O. Pulmonary abnormalities in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol. 1999;104:1031–6.CrossRefPubMed
12.
go back to reference Busse PJ, Razvi S, Cunningham-Rundles C. Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2002;109:1001–4.CrossRefPubMed Busse PJ, Razvi S, Cunningham-Rundles C. Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2002;109:1001–4.CrossRefPubMed
13.
go back to reference Aghamohammadi A, Allahverdi A, Abolhassani H, Moazzami K, Alizadeh H, Gharagozlou M, et al. Comparison of pulmonary diseases in common variable immunodeficiency and X-linked agammaglobulinaemia. Respirology. 2010;15:289–95.CrossRefPubMed Aghamohammadi A, Allahverdi A, Abolhassani H, Moazzami K, Alizadeh H, Gharagozlou M, et al. Comparison of pulmonary diseases in common variable immunodeficiency and X-linked agammaglobulinaemia. Respirology. 2010;15:289–95.CrossRefPubMed
14.
go back to reference Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011;31:315–22.CrossRefPubMed Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011;31:315–22.CrossRefPubMed
15.
go back to reference 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(1354–60): e4. 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(1354–60): e4.
16.
go back to reference Kuruvilla M, de la Morena MT. Antibiotic prophylaxis in primary immune deficiency disorders. J Allergy Clin Immunol Pract. 2013;1:573–82.CrossRefPubMed Kuruvilla M, de la Morena MT. Antibiotic prophylaxis in primary immune deficiency disorders. J Allergy Clin Immunol Pract. 2013;1:573–82.CrossRefPubMed
17.
go back to reference Riffenburgh RH. Chapter 6 - statistical testing, risks, and odds in medical decisions. In: Riffenburgh RH, editor. Statistics in Medicine. 2nd ed. Burlington: Academic Press; 2006. p. 93–114.CrossRef Riffenburgh RH. Chapter 6 - statistical testing, risks, and odds in medical decisions. In: Riffenburgh RH, editor. Statistics in Medicine. 2nd ed. Burlington: Academic Press; 2006. p. 93–114.CrossRef
18.
go back to reference Jesenak M, Banovcin P, Jesenakova B, Babusikova E. Pulmonary manifestations of primary immunodeficiency disorders in children. Front Pediatr. 2014;2:77.CrossRefPubMedPubMedCentral Jesenak M, Banovcin P, Jesenakova B, Babusikova E. Pulmonary manifestations of primary immunodeficiency disorders in children. Front Pediatr. 2014;2:77.CrossRefPubMedPubMedCentral
19.
go back to reference Rezaei N, Aghamohammadi A, Siadat SD, Nejati M, Ahmadi H, Moin M, et al. Serum bactericidal antibody response to serogroup C polysaccharide meningococcal vaccination in children with primary antibody deficiencies. Vaccine. 2007;25:5308–14.CrossRefPubMed Rezaei N, Aghamohammadi A, Siadat SD, Nejati M, Ahmadi H, Moin M, et al. Serum bactericidal antibody response to serogroup C polysaccharide meningococcal vaccination in children with primary antibody deficiencies. Vaccine. 2007;25:5308–14.CrossRefPubMed
20.
go back to reference Aguilar C, Malphettes M, Donadieu J, Chandesris O, Coignard-Biehler H, Catherinot E, et al. Prevention of infections during primary immunodeficiency. Clin Infect Dis. 2014;59:1462–70.CrossRefPubMed Aguilar C, Malphettes M, Donadieu J, Chandesris O, Coignard-Biehler H, Catherinot E, et al. Prevention of infections during primary immunodeficiency. Clin Infect Dis. 2014;59:1462–70.CrossRefPubMed
21.
go back to reference Hermaszewski RA, Webster AD. Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications. Q J Med. 1993;86:31–42.PubMed Hermaszewski RA, Webster AD. Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications. Q J Med. 1993;86:31–42.PubMed
22.
go back to reference Mikolajczyk MG, Concepcion NF, Wang T, Frazier D, Golding B, Frasch CE, et al. Characterization of antibodies to capsular polysaccharide antigens of Haemophilus influenzae type b and Streptococcus pneumoniae in human immune globulin intravenous preparations. Clin Diagn Lab Immunol. 2004;11:1158–64.PubMedPubMedCentral Mikolajczyk MG, Concepcion NF, Wang T, Frazier D, Golding B, Frasch CE, et al. Characterization of antibodies to capsular polysaccharide antigens of Haemophilus influenzae type b and Streptococcus pneumoniae in human immune globulin intravenous preparations. Clin Diagn Lab Immunol. 2004;11:1158–64.PubMedPubMedCentral
23.
go back to reference Lee S, Kim HW, Kim KH. Functional antibodies to Haemophilus influenzae type B, Neisseria meningitidis, and Streptococcus pneumoniae contained in intravenous immunoglobulin products. Transfusion. 2017;57:157–65.CrossRefPubMed Lee S, Kim HW, Kim KH. Functional antibodies to Haemophilus influenzae type B, Neisseria meningitidis, and Streptococcus pneumoniae contained in intravenous immunoglobulin products. Transfusion. 2017;57:157–65.CrossRefPubMed
24.
go back to reference 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; 136:1186–205.e1–78. 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; 136:1186–205.e1–78.
25.
go back to reference Kainulainen L, Vuorinen T, Rantakokko-Jalava K, Osterback R, Ruuskanen O. Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol. 2010;126:120–6.CrossRefPubMedPubMedCentral Kainulainen L, Vuorinen T, Rantakokko-Jalava K, Osterback R, Ruuskanen O. Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol. 2010;126:120–6.CrossRefPubMedPubMedCentral
26.
go back to reference 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;125:1354-60.e4.CrossRefPubMed 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;125:1354-60.e4.CrossRefPubMed
27.
go back to reference Brent J, Guzman D, Bangs C, Grimbacher B, Fayolle C, Huissoon A, et al. Clinical and laboratory correlates of lung disease and cancer in adults with idiopathic hypogammaglobulinaemia. Clin Exp Immunol. 2016;184:73–82.CrossRefPubMedPubMedCentral Brent J, Guzman D, Bangs C, Grimbacher B, Fayolle C, Huissoon A, et al. Clinical and laboratory correlates of lung disease and cancer in adults with idiopathic hypogammaglobulinaemia. Clin Exp Immunol. 2016;184:73–82.CrossRefPubMedPubMedCentral
28.
go back to reference Urm SH, Yun HD, Fenta YA, Yoo KH, Abraham RS, Hagan J, et al. Asthma and risk of selective IgA deficiency or common variable immunodeficiency: a population-based case-control study. Mayo Clin Proc. 2013;88:813–21.CrossRefPubMed Urm SH, Yun HD, Fenta YA, Yoo KH, Abraham RS, Hagan J, et al. Asthma and risk of selective IgA deficiency or common variable immunodeficiency: a population-based case-control study. Mayo Clin Proc. 2013;88:813–21.CrossRefPubMed
29.
go back to reference Juhn YJ, Kita H, Yawn BP, Boyce TG, Yoo KH, McGree ME, et al. Increased risk of serious pneumococcal disease in patients with asthma. J Allergy Clin Immunol. 2008;122:719–23.CrossRefPubMedPubMedCentral Juhn YJ, Kita H, Yawn BP, Boyce TG, Yoo KH, McGree ME, et al. Increased risk of serious pneumococcal disease in patients with asthma. J Allergy Clin Immunol. 2008;122:719–23.CrossRefPubMedPubMedCentral
30.
go back to reference Wong GK, Huissoon AP. T-cell abnormalities in common variable immunodeficiency: the hidden defect. J Clin Pathol. 2016;69:672–6.CrossRefPubMed Wong GK, Huissoon AP. T-cell abnormalities in common variable immunodeficiency: the hidden defect. J Clin Pathol. 2016;69:672–6.CrossRefPubMed
31.
go back to reference Paquin-Proulx D, Sandberg JK. Persistent immune activation in CVID and the role of IVIg in its suppression. Front Immunol 2014; 5:637-. Paquin-Proulx D, Sandberg JK. Persistent immune activation in CVID and the role of IVIg in its suppression. Front Immunol 2014; 5:637-.
32.
go back to reference Lawrence MG, Palacios-Kibler TV, Workman LJ, Schuyler AJ, Steinke JW, Payne SC, et al. Low serum IgE is a sensitive and specific marker for common variable immunodeficiency (CVID). J Clin Immunol. 2018;38:225–33.CrossRefPubMedPubMedCentral Lawrence MG, Palacios-Kibler TV, Workman LJ, Schuyler AJ, Steinke JW, Payne SC, et al. Low serum IgE is a sensitive and specific marker for common variable immunodeficiency (CVID). J Clin Immunol. 2018;38:225–33.CrossRefPubMedPubMedCentral
Metadata
Title
Risk Factors of Pneumonia in Primary Antibody Deficiency Patients Receiving Immunoglobulin Therapy: Data from the US Immunodeficiency Network (USIDNET)
Authors
Maha N. Syed
Carleigh Kutac
Jennifer M. Miller
Rebecca Marsh
Kathleen E. Sullivan
Charlotte Cunningham-Rundles
Ramsay L. Fuleihan
Farrah Kheradmand
Joud Hajjar
Publication date
02-07-2022
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 7/2022
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-022-01317-2

Other articles of this Issue 7/2022

Journal of Clinical Immunology 7/2022 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.