Bronchiolitis obliterans syndrome, hypogammaglobulinemia, and infectious complications of lung transplantation

https://doi.org/10.1016/j.healun.2012.10.006Get rights and content

Background

Because infection has been associated with the development of bronchiolitis obliterans syndrome (BOS), we hypothesized that post-transplant hypogammaglobulinemia would be associated with infection and BOS.

Methods

Cross-sectional levels of serum immunoglobulins were measured on 2 occasions in our transplant cohort and models developed to explain serum immunoglobulin levels and BOS-free survival.

Results

A total of 139 patients (median age, 46.6 years) were evaluated at 47 months (range, 15–74 months) after transplant, and 87 were re-evaluated at 72 months (40–107 months). Of this cohort, 44% were immunoglobulin (Ig) G deficient and levels remained stable across the study period, and 27% were IgA deficient and levels fell slightly over time (p = 0.003). Both immunoglobulin classes were lower in patients with a history of invasive fungal infection, whereas IgA levels were lower in patients with a history of community-acquired respiratory viral infection. Low IgG was independently associated with shorter BOS-free survival (hazard ratio, 0.79; 95% confidence interval, 0.71–0.88; p<0.001).

Conclusion

Serum immunoglobulin deficiency is common after lung transplantation and is associated with community-acquired respiratory viral infection, invasive fungal infection, and BOS.

Section snippets

Methods

The study was approved by The Prince Charles Hospital Human Research and Ethics Committee.

Results

Full demographic data for the cohort are reported in Supplementary Table 1 (available on the JHLTonline.org Web site). Patients (48% women) were a median age of 46.6 years (IQR, 31.0–56.7 years) at transplantation. The diagnosis was cystic fibrosis in 34% and chronic obstructive pulmonary disease (COPD) in 37%. The transplant procedures were bilateral in 86%, single-lung in 7%, heart-lung in 5%, and heart-lung-liver in 2%. At the census, 51% of the cohort had a diagnosis of BOS grade≥ 1.

Discussion

We have found that serum IgG and IgA levels both fall after transplantation, with many patients having levels below the reference range, and that immunoglobulin deficiency places the lung transplant recipient at risk of CARV infection, invasive fungal infection, and BOS. Our findings suggest that immunoglobulin deficiency should be excluded in any patient presenting with 1 or more of these post-transplant complications.

Several groups have identified a similarly high prevalence (48% to 73%) of

Disclosure statement

The authors thank Jonathan Bleier, Biostatistician from Queensland Institute of Medical Research, for statistical advice and support.

Some of this work was presented at the Thirtieth Anniversary Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation, Chicago, Illinois, April 20–24, 2010.

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to

References (19)

  • S. Husain et al.

    A 2010 working formulation for the standardization of definitions of infections in cardiothoracic transplant recipients

    J Heart Lung Transplant

    (2011)
  • M. Estenne et al.

    Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria

    J Heart Lung Transplant

    (2002)
  • A.R. Glanville et al.

    Severity of lymphocytic bronchiolitis predicts long-term outcome after lung transplantation

    Am J Respir Crit Care Med

    (2008)
  • J. Gottlieb et al.

    Community-acquired respiratory viral infections in lung transplant recipients: a single season cohort study

    Transplantation

    (2009)
  • A.P. Khalifah et al.

    Respiratory viral infections are a distinct risk for bronchiolitis obliterans syndrome and death

    Am J Respir Crit Care Med

    (2004)
  • S.S. Weigt et al.

    Aspergillus colonization of the lung allograft is a risk factor for bronchiolitis obliterans syndrome

    Am J Transplant

    (2009)
  • F. Backhed et al.

    Host-bacterial mutualism in the human intestine

    Science

    (2005)
  • J. Robertson et al.

    Hypogammaglobulinemia: Incidence, risk factors, and outcomes following pediatric lung transplantation

    Pediatr Transplant

    (2009)
  • N.S. Goldfarb et al.

    Hypogammaglobulinemia in lung transplant recipients

    Transplantation

    (2001)
There are more references available in the full text version of this article.

Cited by (25)

  • Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees

    2022, Journal of Allergy and Clinical Immunology
    Citation Excerpt :

    Risk factors for post-LT SHG include basiliximab induction or mycophenolate use.24,252 Risk factors for post-LT severe SHG include female sex, COPD/emphysema, bronchiolitis obliterans, and less than 30% of pretransplant pneumococcal antibody levels being protective.24,252-254,256 Immune evaluation may be particularly warranted for patients undergoing LT for CF and COPD.

  • Low pretransplant IgA level is associated with early post–lung transplant seromucous infection

    2018, Journal of Thoracic and Cardiovascular Surgery
    Citation Excerpt :

    However, in this paper, we focused on the possibility of pretransplant susceptibility (or predisposition) to posttransplant infection. IgA deficiency before lung transplantation has not been well studied, although it has been suggested that posttransplant IgA deficiency is associated with increased community-acquired pneumonia, invasive fungal infection, sepsis, and death.5,22 This is hypothesized to be secondary to weakened seromucous defenses.

  • Monitoring of early humoral immunity to identify lung recipients at risk for development of serious infections: A multicenter prospective study

    2018, Journal of Heart and Lung Transplantation
    Citation Excerpt :

    Goldfarb et al8 demonstrated that IgG hypogammaglobulinemia was a risk factor for opportunistic infections. Chambers et al4 described lower IgG levels in lung recipients with fungal infections. This association was also suggested by Robertson et al5 in pediatric lung transplantation.

  • Guardians of the Gut: Pretransplant IgA levels and seromucous infections

    2018, Journal of Thoracic and Cardiovascular Surgery
View all citing articles on Scopus
View full text