Immune response to influenza vaccination in children and adults with asthma: effect of corticosteroid therapy

doi:10.1016/j.jaci.2003.12.584

Journal of Allergy and Clinical Immunology

Volume 113, Issue 4, April 2004, Pages 717-724

https://doi.org/10.1016/j.jaci.2003.12.584 Get rights and content

Abstract

Background

Annual influenza vaccination is currently recommended as a preventative measure for all patients with asthma. However, the effect of maintenance corticosteroid therapy on the immune response to influenza vaccine has received limited evaluation.

Objective

In this study, we evaluated the effect of corticosteroid therapy on the immune response to influenza vaccine in children and adults with asthma.

Methods

This was a substudy of a larger multicenter, randomized, double-masked, placebo-controlled, crossover study investigating the safety of trivalent influenza vaccine in patients with asthma. At baseline, 294 subjects were randomized to receive either placebo first (n = 139) or inactivated trivalent split-virus influenza vaccine first (n = 155). Study subjects were categorized into 2 groups: subjects in group 1 (n = 148) were receiving medium-dose or high-dose inhaled corticosteroids (ICSs) or oral corticosteroids, whereas subjects in group 2 (n = 146) were not receiving corticosteroids or were receiving low-dose ICSs. Serum hemagglutination inhibition antibody titers for the vaccine antigens were measured before and 4 weeks after the administration of placebo or vaccine.

Results

Serologic responses to each influenza vaccine antigen were significantly higher in vaccine than in placebo recipients and were similar among influenza vaccine recipients in groups 1 and 2 for the following endpoints: rise in antibody titer, percent of participants who developed a serological response, and percent of subjects who developed a serum hemagglutination inhibition antibody titer ≥1:32. Post hoc subgroup analyses demonstrated an attenuated response to influenza B antigen in subjects receiving high-dose ICS compared with subjects who were steroid-naïve (P<.05).

Conclusion

The immune response to the A antigens of the inactivated influenza vaccine in subjects with asthma is not adversely affected by ICS therapy. High-dose ICS therapy may diminish the response to the B antigen of the vaccine, an observation that needs further investigation.

Section snippets

Patients

This was a prospective study performed as a substudy of a larger multicenter, randomized crossover trial investigating the safety of year 2000 trivalent inactivated split-virus influenza vaccine in children and adults with asthma (n = 2032).¹⁴ A total of 294 subjects were recruited during the first arm of the main study (ie, before crossover) from 6 of 19 of the centers of the American Lung Association Asthma Clinical Research Centers network during the study period, September 2000 through

Patients

A total of 294 participants were eligible and consented for the study. Of these, 155 were randomized to receive the influenza vaccine first and 139 to placebo first. Of these, 15 participants from the vaccine group and 7 from the placebo group were dropped because of protocol violations (blood specimens were not received, only 1 specimen was received, or the patient did not come back for follow-up). Data from the remaining 272 participants (vaccine group, n = 140; placebo group, n = 132) were

Discussion

We have previously demonstrated the safety of inactivated influenza vaccination in a large cohort of children and adults with asthma.¹⁴ In this substudy, we found that the chronic use of ICS in these patients did not adversely affect the humoral immune response to influenza A (H1N1, H3N2) vaccine antigens. Similarly, in the primary analysis of the humoral responses to the influenza B antigen, no effect of chronic ICS use was seen. However, results of our post hoc subgroup analysis suggest that

Acknowledgements

The Asthma Clinical Research Centers investigators would like to thank David M. Shade, JD, RPFT, for his help in compiling the data for this project, the American Lung Association, and the following organizations that provided grant support for this study: the American Lung Associations of Alabama, Central Florida, Colorado, Delaware, Eastern Missouri, Florida, Georgia, Gulfcoast Florida, Hudson Valley, Indiana, Louisiana, Maine, Metropolitan Chicago, Mid-Ohio, Minnesota, Nassua-Suffolk, New

References (38)

S Kondo et al.
The effects of influenza virus infection on FEV₁ in asthmatic children
Chest
(1991)
K Neuzil
Influenza vaccine in children with asthma: why no progress?
J Pediatr
(2001)
K Neuzil et al.
The burden of influenza illness in children with asthma and other chronic medical conditions
J Pediatr
(2000)
T.D Bell et al.
Immunization with killed influenza virus in children with chronic asthma
Chest
(1978)
S.A Halperin et al.
Safety and immunogenicity of trivalent, inactivated, mammalian cell culture-derived influenza vaccine in healthy adults, seniors, and children
Vaccine
(2002)
A.M Iorio et al.
Immunogenicity of influenza vaccine (1993-94 winter season) in HIV-seropositive and seronegative ex-intravenous drug users
Vaccine
(1997)
N.A Hanania et al.
Adverse effects of inhaled corticosteroids
Am J Med
(1995)
H.W Kelly
Potential adverse effects of the inhaled corticosteroids
J Allergy Clin Immunol
(2003)
D Revicki et al.
Integrating patient preferences into health outcomes assessment: the multiattribute Asthma Symptom Utility Index
Chest
(1998)
W.D Dupont et al.
Power and sample size calculations: a review and computer program
Control Clin Trials
(1990)

W.A Keitel et al.

Inactivated influenza vaccines

R Lambkin et al.

Rapid antibody response to influenza vaccination in an “at risk” group

Vaccine

(2000)

M.A Kubiet et al.

Serum antibody response to influenza vaccine in pulmonary patients receiving corticosteroids

Chest

(1996)

W.H Barker

Excess pneumonia and influenza associated hospitalization during influenza epidemics in the United States

Am J Public Health

(1986)

K.M Sullivan et al.

Estimates of the US health impact of influenza

Am J Public Health

(1993)

K.M Neuzil et al.

The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children

N Engl J Med

(2000)

H.S Izurieta et al.

Influenza and the rates of hospitalization for respiratory disease among infants and young children

N Engl J Med

(2000)

W.P Glezen et al.

Impact of respiratory virus infections on persons with underlying conditions

JAMA

(2000)

N Sugaya et al.

Efficacy of inactivated influenza vaccine in preventing antigenically drifted influenza type A and well-matched type B

JAMA

(1994)

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The effect of inhaled corticosteroids (ICS) and biologics on the humoral immune response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in patients with asthma is unknown. We prospectively evaluated the humoral immune response 3 weeks (T1) and 6 months (T2) after the second dose of BNT162b2 in 30 SARS-CoV-2-naïve patients with asthma. We measured anti-spike immunoglobulin G (IgG) titers and serum-neutralizing activity against the ancestral SARS-CoV-2 strain. The anti-spike IgG titer and neutralizing activity did not differ significantly between the biologics and non-biologics groups at T1 (P = 0.708 and P = 0.417, respectively) or T2 (P = 0.299 and P = 0.492, respectively). In the multivariate analysis, age and sex were significantly associated with the magnitude of the humoral immune response; however, the use of biologics and ICS dose were not, suggesting that these would not affect BNT162b2 immunogenicity in patients with asthma. Larger studies are needed to validate these findings.
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Despite their widespread clinical use, oral corticosteroids (OCSs) are well known to be associated with a myriad of adverse effects, including immunosuppression. By inhibiting transcription factors and affecting leukocyte function, prolonged OCS use leads to significant CD4 lymphopenia and often a decrease in serum immunoglobulin (Ig)G. Conversely, OCS use has minimal impact on circulating B cell, serum IgM, or serum IgA levels. Although there is a paucity of literature, individuals treated with prolonged OCS seem to typically maintain humoral response to various vaccinations despite hypogammaglobinemia, but this area warrants additional research, especially in the setting of the coronavirus disease 2019 pandemic. Individuals treated with prolonged OCS use are most at risk for opportunistic infections, especially those with underlying malignancy and history of bone marrow transplant. Risk mitigation strategies to decrease infectious complication with OCS use include limiting the dose and duration of therapy, appropriately completing a full vaccination series, consideration for passive immunization, and prophylaxis against opportunistic infections.
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Earlier data regarding corticosteroid use and influenza infection has been inconsistent. While some studies have found that patients receiving inhaled or systemic corticosteroids may have a decreased immune response to influenza vaccination and thus may be more susceptible to influenza [16,17], others have shown no such decrease [18–21]. We recently found that vaccinated patients who received a large joint (hip, knee, shoulder) corticosteroid injection had an increased risk of influenza compared to unmatched vaccinated controls [13].
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To examine odds of influenza in patients who received spinal region CSI compared to matched controls.
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Adults (n=9,196) who received a spinal CSI (epidural, facet, sacroiliac, paravertebral block) during influenza seasons occurring from 2000 to 2020 were 1:1 matched to controls without spinal CSI.
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A total of 9,196 adults (mean age 60.8 years, 60.4% female) received a spinal CSI and were matched to a control. There were no increased odds of influenza for spinal CSI patients as compared to matched controls (OR 1.13, [95% CI, 0.86–1.48]). When subgroups were examined, there were also no increased odds of influenza for spinal CSI patients based on immunization status (unvaccinated or vaccinated) or spinal injection location (epidural or non-epidural).
Spinal region CSI was not associated with increased odds of influenza or reduced vaccine efficacy. This is reassuring given the analgesic and functional restoration benefits of these injections. Assessing risk of viral infection associated with spinal CSI is particularly relevant in the era of the COVID-19 pandemic, and further work is needed to address this issue.
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The steroid doses varied from the daily equivalent of 2.5–60 mg of prednisone, with no correlation with antibody response. In a larger multicenter, randomized, placebo-controlled study of children and adults with asthma, trivalent influenza vaccination with systemic CS use was evaluated, and the subjects were separated into groups based on a low or no CS dose (group 1) and a moderate-to-high CS dose (group 2).19 Primary study endpoints demonstrated an adequate immune response (>4-fold rise in baseline antibody), which was similar in both groups that received vaccination for influenza (A and B), and chronic systemic CS use did not diminish this effect.
Corticosteroid injection (CSI) is a commonly used tool in hand surgery that is often given little consideration as a potential detriment to vaccination efficacy. The authors reviewed guidelines issued by relevant societies for the timing of CSI around the severe acute respiratory syndrome coronavirus 2 vaccination period and the evidence used to support them. Ultimately, providers and patients should be adequately educated on the theoretical risks and benefits before proceeding with CSI immediately before, during, or immediately after coronavirus disease 2019 vaccination.
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Infectious Complications of Corticosteroid Therapy
2018, Principles and Practice of Pediatric Infectious Diseases

View all citing articles on Scopus

^☆

Supported by the American Lung Association.

Presented at the American Thoracic Society Annual Meeting, Atlanta, Ga, May 2002.

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Basic and clinical immunologyImmune response to influenza vaccination in children and adults with asthma: effect of corticosteroid therapy☆

Abstract

Background

Objective

Methods

Results

Conclusion

Section snippets

Patients

Patients

Discussion

Acknowledgements

Chest

J Pediatr

J Pediatr

Chest

Vaccine

Vaccine

Am J Med

J Allergy Clin Immunol

Chest

Control Clin Trials

Vaccine

Chest

Excess pneumonia and influenza associated hospitalization during influenza epidemics in the United States

Am J Public Health

Estimates of the US health impact of influenza

Am J Public Health

The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children

N Engl J Med

Influenza and the rates of hospitalization for respiratory disease among infants and young children

N Engl J Med

Impact of respiratory virus infections on persons with underlying conditions

JAMA

Efficacy of inactivated influenza vaccine in preventing antigenically drifted influenza type A and well-matched type B

JAMA

Basic and clinical immunology
Immune response to influenza vaccination in children and adults with asthma: effect of corticosteroid therapy☆