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IgE Sensitization to Aspergillus fumigatus Is Not a Bystander Phenomenon in Cystic Fibrosis Lung DiseaseAspergillus fumigatus in Cystic Fibrosis FREE TO VIEW

Marijke Peetermans, MD; Pieter Goeminne, MD, PhD; Christiane De Boeck, MD, PhD; Lieven J. Dupont, MD, PhD
Author and Funding Information

From the Department of Internal Medicine (Dr Peetermans), the Department of Respiratory Medicine (Drs Goeminne and Dupont), and the Department of Pediatrics (Dr De Boeck), University Hospital Leuven, Katholieke Universiteit Leuven.

CORRESPONDENCE TO: Lieven J. Dupont, MD, PhD, Respiratory Medicine, Herestraat 49, B-3000 Leuven, Belgium; e-mail: lieven.dupont@uzleuven.be


FUNDING/SUPPORT: This work was supported by a grant of the Fonds Alphonse en Jean Forton of the Koning Boudewijnstichting, Belgium. Dr Dupont is a part-time senior research fellow of the FWO Vlaanderen.

FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(3):e99-e100. doi:10.1378/chest.14-0635
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To the Editor:

We have read with great interest the article by Baxter et al1 in CHEST (May 2013) highlighting the importance of sensitization to Aspergillus fumigatus (Af) in progression of cystic fibrosis (CF) lung disease. We and many others have previously reported that sensitization to Af is frequent in patients with CF: It was observed in 31% of the patient cohort (n = 153) who were followed up at the Leuven CF referral center.2 We also confirmed significantly impaired lung function parameters in Af-sensitized compared with Af-nonsensitized patients, with an average difference in FEV1 of 19 ± 4% predicted. In a multivariate analysis with age, sex, BMI, Pseudomonas aeruginosa colonization, pancreatic insufficiency, and gastroesophageal reflux disease as covariates, a significantly lower FEV1 and vital capacity (P < .001) was associated with Af sensitization, as well as an increased airway resistance (P < .05) and hyperinflation (higher residual volume, P < .001) (e-Table 1). Interestingly, no significant differences in lung function parameters were found between patients with serologic criteria for allergic bronchopulmonary aspergillosis (ABPA) (n = 17) and patients with sensitization to Af without ABPA. Similar to the data presented by Baxter et al1 and others,3 we observed, in a 3-year period, more exacerbations in Af-sensitized patients with CF compared with patients without sensitization to Af (5.30 ± 4.54 vs 1.69 ± 2.78 hospital admissions for IV antibiotic therapy, respectively; P < .005).

The group of Baxter and Dunn has recently proposed a novel classification of Aspergillus disease in patients with CF.4 However, interesting from a pathophysiologic point of view and to guide further therapeutic trials, our data on pulmonary function and exacerbation rate show significant differences only for Af-sensitized vs nonsensitized patients. If we reclassified the nonsensitized patients in two groups taking into account the absence or presence of Af IgG, no significant differences were seen between “nondiseased” and “Af-bronchitis” patients.

To date, most evidence has, thus, emerged for the role of Af sensitization, which raises the question if treatment of Af-sensitized patients, even before ABPA is present, could result in better outcomes. The rationale would be to lower Af allergenic burden and/or to inhibit the resulting hypersensitivity response, before pulmonary function decline or ABPA develop. Whether such a treatment should consist of antifungal therapy, as in the pivotal Fungal Asthma Sensitization Trial (FAST) in severe asthma5 or should aim to prevent the IgE-mediated hypersensitivity remains to be elucidated. A placebo-controlled intervention study evaluating monitored antifungal treatment (itraconazole, voriconazole), early treatment with anti-IgE therapies such as omalizumab, or perhaps a combination of both seems indicated in Af-sensitized patients with CF.

Acknowledgments

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Additional information: The e-Table can be found in the Supplemental Materials section of the online article.

Baxter CG, Moore CB, Jones AM, Webb AK, Denning DW. IgE-mediated immune responses and airway detection ofAspergillusandCandidain adult cystic fibrosis. Chest. 2013;143(5):1351-1357. [CrossRef] [PubMed]
 
Peetermans M, Goeminne PC, De Boeck K, Dupont LJ. Impact of sensitization toAspergillus fumigatuson lung function in cystic fibrosis. Paper presented at: e-Communication session at the European Respiratory Society Annual Congress; September 20, 2010; Barcelona, Spain.
 
Fillaux J, Brémont F, Murris M, et al. Assessment ofAspergillussensitization or persistent carriage as a factor in lung function impairment in cystic fibrosis patients. Scand J Infect Dis. 2012;44(11):842-847. [CrossRef] [PubMed]
 
Baxter CG, Dunn G, Jones AM, et al. Novel immunologic classification of aspergillosis in adult cystic fibrosis. J Allergy Clin Immunol. 2013;132(3):560-566. [CrossRef] [PubMed]
 
Denning DW, O’Driscoll BR, Powell G, et al. Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: the Fungal Asthma Sensitization Trial (FAST) study. Am J Respir Crit Care Med. 2009;179(1):11-18. [CrossRef] [PubMed]
 

Figures

Tables

References

Baxter CG, Moore CB, Jones AM, Webb AK, Denning DW. IgE-mediated immune responses and airway detection ofAspergillusandCandidain adult cystic fibrosis. Chest. 2013;143(5):1351-1357. [CrossRef] [PubMed]
 
Peetermans M, Goeminne PC, De Boeck K, Dupont LJ. Impact of sensitization toAspergillus fumigatuson lung function in cystic fibrosis. Paper presented at: e-Communication session at the European Respiratory Society Annual Congress; September 20, 2010; Barcelona, Spain.
 
Fillaux J, Brémont F, Murris M, et al. Assessment ofAspergillussensitization or persistent carriage as a factor in lung function impairment in cystic fibrosis patients. Scand J Infect Dis. 2012;44(11):842-847. [CrossRef] [PubMed]
 
Baxter CG, Dunn G, Jones AM, et al. Novel immunologic classification of aspergillosis in adult cystic fibrosis. J Allergy Clin Immunol. 2013;132(3):560-566. [CrossRef] [PubMed]
 
Denning DW, O’Driscoll BR, Powell G, et al. Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: the Fungal Asthma Sensitization Trial (FAST) study. Am J Respir Crit Care Med. 2009;179(1):11-18. [CrossRef] [PubMed]
 
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