Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb 27;19(1):15.
doi: 10.1186/s13223-023-00760-z.

Association between Cystic Fibrosis exacerbations, lung function, T2 inflammation and microbiological colonization

Dana Albon  1 , Lijia Zhang  2 , James Patrie  3 , Marieke Jones  3 , Z Galvin Li  4 , Emily Noonan  5 , Larry Borish  5   6
Affiliations

Association between Cystic Fibrosis exacerbations, lung function, T2 inflammation and microbiological colonization

Dana Albon et al. Allergy Asthma Clin Immunol. .

Abstract

Background: The Cystic Fibrosis Foundation Patient Registry (CFFPR) reports a high prevalence of asthma (34.6%) in people with Cystic Fibrosis (PwCF). While our current understanding of this relationship is limited, a type 2 inflammatory (T2) phenotype has often been identified in CF patients.

Research question: This study aimed to evaluate the relationship between the eosinophilic CF T2 inflammatory phenotype and CF-related pulmonary outcomes and microbiological data.

Study design and methods: We conducted a retrospective chart review of adult patients with CF (18 and older; n = 93) receiving their care at University of Virginia Medical Center adult program from January, 2013 through December, 2018. Data collected included demographic data, CFTR (CF transmembrane conductance regulator) mutation, CF comorbidities, medications, Absolute Eosinophil Counts (AEC) in cells/µL and Immunoglobulin E (IgE) levels in IU/mL.

Results: Of 93 patients screened for study eligibility, 74 were included in the final analysis; 19 patients were excluded due to lack of longitudinal data across the study timeline. Lung function decline correlated with increased AEC (p < 0.001) and IgE (p < 0.001) even when adjusting for covariates: age, gender, presence of Pseudomonas spp., MRSA, other bacterial spp., Aspergillus spp., and other fungi (p < 0.001). Univariate analysis demonstrated that people with CF who experienced more than 2 exacerbations requiring hospitalizations and/or intravenous antibiotics a year were more likely to have high AEC (p = 0.018). Logistic regression showed that as AEC increases, the probability that the measurement was taken during a CF exacerbation increases (p = 0.0039). A linear mixed model showed that each additional annual exacerbation event increased on average the log IgE by 0.04. (p = 0.015). This finding remained stable in a multivariate model (p = 0.0145). When adjusted for atopy, log IgE increases as the number of exacerbation events increases (p = 0.022). There was no association between AEC and IgE and microbiological colonization.

Interpretation: This study has shown that in CF patients, T2 inflammation based on serum AEC and IgE correlated with pulmonary exacerbations requiring hospitalizations and/or intravenous antibiotics, independent of bacterial airway colonization. In addition, lung function decline correlated with increased IgE and AEC. Further studies are needed to explore these correlations and potential impact on treatment.

Keywords: Bacteria; Cystic fibrosis; Eosinophil; Fungi; Immunoglobulin E; Pulmonary exacerbation; Type 2 inflammation.

PubMed Disclaimer

Conflict of interest statement

No relevant conflicts exist for Dr. Dana Albon, Dr. Lijia Zhang, James Patrie, Dr. Marieke Jones, Galvin Li, Emily Noonan, and Dr. Larry Borish.

Figures

Fig. 1
Fig. 1
Relationship between lung function (ppFEV1) and AEC and IgE. Image on the left A linear mixed model showed a statistically significant relationship between ppFEV1 decline and log AEC increase (p < 0.001) Image on the right: A linear mixed model showed a statistically significant relationship between ppFEV1 decline and log IgE increase (p < 0.001). ppFEV1 = percent predicted Forced Expiratory Volume in 1 s. AEC = absolute eosinophil count IgE = Immunoglobulin E
Fig. 2
Fig. 2
A. Pulmonary exacerbations, AEC and IgE. AEC = Absolute Eosinophil Count; highest annual AEC value averaged per year/per person over the study period was used to calculate median and interquartile range for AEC for each subgroup. *Greater AEC was a significant predictor of greater number of pulmonary exacerbation episodes (POR: 1.88; 95% CI [1.14, 3.08], p = 0.013). B. IgE = Immunoglobulin E; highest annual IgE value averaged per year per person over the study period was used to calculate median and interquartile range IgE for each subgroup
Fig. 3
Fig. 3
Pulmonary exacerbations and AEC logistic regression: as log AEC increases, the probability that the measurement was taken during a CF exacerbation increases (p = 0.0039) AEC = Absolute Eosinophil Count
Fig. 4
Fig. 4
IgE and Pulmonary exacerbations: Increased log IgE correlates with increased numbers of annual CF exacerbations (p = 0.0015). IgE = Immunoglobulin E
Fig. 5
Fig. 5
Pulmonary exacerbations and IgE in presence of atopy (positive respiratory allergen or fungus allergen IgE panels) An increase in log IgE is noticed with each additional annual exacerbation (p = 0.0044) and significantly higher log IgE in allergen positive patients (p < 0.001). IgE = Immunoglobulin E
See this image and copyright information in PMC

References

    1. Cystic Fibrosis Foundation. Cystic Fibrosis Foundation. United States, 2019.
    1. Fahy JV. Type 2 inflammation in asthma–present in most, absent in many. Nat Rev Immunol. 2015;15(1):57–65. doi: 10.1038/nri3786.PMID:25534623;PMCID:PMC4390063. - DOI - PMC - PubMed
    1. Zhang L, Borish L, Smith A, Somerville L, Albon D. Use of mepolizumab in adult patients with cystic fibrosis and an eosinophilic phenotype: case series. Allergy Asthma Clin Immunol. 2020;6(16):3. doi: 10.1186/s13223-019-0397-3.PMID:31921321;PMCID:PMC6945791. - DOI - PMC - PubMed
    1. Voehringer D, Reese TA, Huang X, Shinkai K, Locksley RM. Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system. J Exp Med. 2006;203(6):1435–1446. doi: 10.1084/jem.20052448. - DOI - PMC - PubMed
    1. Munitz A, Brandt EB, Mingler M, Finkelman FD, Rothenberg ME. Distinct roles for IL-13 and IL-4 via IL-13 receptor alpha1 and the type II IL-4 receptor in asthma pathogenesis. Proc Natl Acad Sci USA. 2008;105(20):7240–7245. doi: 10.1073/pnas.0802465105. - DOI - PMC - PubMed

LinkOut - more resources