Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
  • Alerts
  • Subscriptions

Bronchodilator responsiveness in children with cystic fibrosis and allergic bronchopulmonary aspergillosis

Mordechai Pollak, Michelle Shaw, David Wilson, Hartmut Grasemann, Felix Ratjen
European Respiratory Journal 2020 56: 2000175; DOI: 10.1183/13993003.00175-2020
Mordechai Pollak
1Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mordechai Pollak
  • For correspondence: morduchp@gmail.com
Michelle Shaw
2Translational Medicine, Sickkids Research Institute, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Wilson
1Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hartmut Grasemann
1Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada
2Translational Medicine, Sickkids Research Institute, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Felix Ratjen
1Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada
2Translational Medicine, Sickkids Research Institute, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

CF patients with a new diagnosis of ABPA had a similar BD response, compared to CF patients with acute lung function deterioration from other causes. BD response testing did not help differentiating ABPA from other causes of lung function deterioration. https://bit.ly/39Oegnh

To the Editor:

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease that occurs in approximately 9% of children with cystic fibrosis (CF) [1]. While ABPA is commonly associated with worsening lung function, differentiating ABPA from other causes of pulmonary function decline often poses a clinical challenge. This is reflected by major differences among the various diagnostic criteria for ABPA that have been suggested to date [2–5]. A positive bronchodilator response (BDR) is characteristic for asthma which is a common co-morbidity in CF patients, but whether this is helpful in differentiating ABPA from other causes of deterioration in lung function is currently unclear. A recent observational study of paediatric CF patients found a significant higher BDR in ABPA compared to patients not sensitised to Aspergillus fumigatus [6]; this stands in contrast to the CF Foundation consensus that did not identify airway obstruction reversibility as a characteristic of CF-related ABPA [5]. We therefore aimed to evaluate the clinical utility of BDR for diagnosis of ABPA in CF by comparing rates of positive BDR prior to a diagnosis of ABPA to CF patients experiencing acute lung function deteriorations for other causes.

This was a retrospective review of all paediatric CF patients diagnosed and treated for ABPA between 2002 and 2018 at The Hospital for Sick Children, Toronto, in whom BDR testing was performed up to 14 days prior to diagnosis of ABPA. The diagnosis was based on CF Foundation consensus criteria: clinical deterioration, elevated IgE, immediate cutaneous reactivity to Aspergillus and recent abnormalities on chest radiograph or computed tomography [5]. We compared those with ABPA to a cohort of CF patients not diagnosed with ABPA, who experienced a drop in forced expiratory volume in 1 s (FEV1) of 10% or more from baseline, matched 3:1 for age, gender and best FEV1 in the previous 6 months. Since our aim was to compare ABPA to all other causes of lung function deterioration, any CF patient with a decline of 10% FEV1 from baseline could be included in the control group. Most of these patients (67 patients; 62%) were diagnosed with a CF pulmonary exacerbation and started on oral (32/67), intravenous (33/67) or inhaled (2/67) antibiotics. From the remaining, 10/41 patients were experiencing symptoms that were interpreted as an acute viral infection, 11/41 were having asthma like symptoms and were treated either by introducing, or encouraging use or stepping up the dose of ICS. The remaining patients were either encouraged to enhance adherence with closer follow-up or introduction of adding mucolytic therapy. BDR was defined as the percent change between pre- and post-inhaled bronchodilator FEV1 % predicted, as calculated using the Global Lung Function Initiative reference equations [7]. A significant BDR was defined as a 12% change or greater from pre- to post-bronchodilator FEV1 [8]. Our standard practise is to ask patients to restrain from any short-acting β-agonist use for at least 4 h and from any long-acting β-agonist (LABA) use for at least 12 h prior to BDR testing.

Clinical characteristics of both groups are summarised in table 1. The ABPA group included 36 patients, of whom 85% had a drop of at least 10% in their FEV1 at the time of diagnosis. Compared to the control group, CF patients with ABPA tended to have a lower FEV1 at baseline and significantly larger drop from baseline on the day of diagnosis (median (interquartile range (IQR)) −23% (−35 to −16%), −18% (−25 to −14%); p=0.05). A higher rate of wheezing was present on examination, and a significantly larger proportion of patients were on inhaled corticosteroids (ICS) (table 1). Two patients in the ABPA group and four in the control group were prescribed a combination of ICS and LABA. There was no significant difference in median (IQR) BDR (4.7% (2.8 to 11.7%) versus 5.2% (−1.2 to 10.5%); p=0.48) or in the proportion of patients with a significant BDR (9/36 (25%), 22/108 (20%); p=0.56) between groups.

View this table:
  • View inline
  • View popup
TABLE 1

Clinical characteristics of patients with allergic bronchopulmonary aspergillosis (ABPA) compared to controls

Since the higher proportion of ICS prior to diagnosis in ABPA patients could potentially mask the BDR response, we compared those prescribed ICS to those who were not. Comparing all patients prescribed ICS, regardless of having ABPA or not, to those without ICS, the proportion of patients with significant BDR was similar (18/69 (26%), 15/75 (20%); p=0.38). Within each group, the proportion of patients with significant BDR was not significantly different having been treated with ICS or not.

These results indicate that paediatric patients with CF initially presenting with ABPA do not differ in their BDR response to CF patients experiencing a fall of 10% from their baseline FEV1, regardless of the cause of deterioration. Overall, the role of BDR testing in CF patients remains not well defined. Levine et al. [9] showed that positivity of BDR testing varies over time and that there was no association with family history of asthma, serum IgE or blood eosinophils. We recently showed that a significant BDR is rare in children with CF treated for pulmonary exacerbations and usually does not lead to immediate change in clinical management [10]. The current study also questions the yield of BDR testing for differentiating ABPA from other causes of lung function deterioration, indicating that the role for routine BDR testing in the care of CF patients seems to be limited.

While ICS are not recommended routinely in CF, a large proportion of the control group (39%) was receiving this medication. This is strikingly similar to the 39% for patients age 6 years and above receiving ICS reported in the 2018 American CF Registry [11]. Reduction of ICS use in CF could potentially have beneficial effects on bacterial and fungal infection rates; further studies are needed to clarify this.

To conclude, in this analysis, paediatric patients with CF initially presenting with ABPA were not more likely to have a BDR greater than seen in patients with other causes of deterioration in their lung function. Thus, we did not find evidence to support the utility of BDR testing in differentiating ABPA from other causes of acute CF exacerbations.

Shareable PDF

Supplementary Material

This one-page PDF can be shared freely online.

Shareable PDF ERJ-00175-2020.Shareable

Footnotes

  • Conflict of interest: M. Pollak has nothing to disclose.

  • Conflict of interest: M. Shaw has nothing to disclose.

  • Conflict of interest: D. Wilson has nothing to disclose.

  • Conflict of interest: H. Grasemann has nothing to disclose.

  • Conflict of interest: F. Ratjen reports grants and personal fees for consultancy from Vertex, personal fees for consultancy from Novartis, Bayer, Roche and Genetech, outside the submitted work.

  • Received January 28, 2020.
  • Accepted March 31, 2020.
  • Copyright ©ERS 2020
https://www.ersjournals.com/user-licence

References

  1. ↵
    1. Maturu VN,
    2. Agarwal R
    . Prevalence of Aspergillus sensitization and allergic bronchopulmonary aspergillosis in cystic fibrosis: systematic review and meta-analysis. Clin Exp Allergy 2015; 45: 1765–1778. doi:10.1111/cea.12595
    OpenUrlCrossRefPubMed
  2. ↵
    1. Rosenberg M
    . Clinical and immunologic criteria for the diagnosis of allergic bronchopulmonary aspergillosis. Ann Intern Med 1977; 86: 405. doi:10.7326/0003-4819-86-4-405
    OpenUrlCrossRefPubMedWeb of Science
    1. Geller DE,
    2. Kaplowitz H,
    3. Light MJ, et al.
    Allergic bronchopulmonary aspergillosis in cystic fibrosis. Chest 1999; 116: 639–646. doi:10.1378/chest.116.3.639
    OpenUrlCrossRefPubMedWeb of Science
    1. Mastella G,
    2. Rainisio M,
    3. Harms HK, et al.
    Allergic bronchopulmonary aspergillosis in cystic fibrosis. A European epidemiological study. Epidemiologic Registry of Cystic Fibrosis. Eur Respir J 2000; 16: 464–471. doi:10.1034/j.1399-3003.2000.016003464.x
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Stevens DA,
    2. Moss RB,
    3. Kurup VP, et al.
    Allergic bronchopulmonary aspergillosis in cystic fibrosis — state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 2003; 37: Suppl. 3, S225–S264. doi:10.1086/376525
    OpenUrlCrossRefPubMedWeb of Science
  4. ↵
    1. Keown K,
    2. Abbott S,
    3. Kuzeljevic B, et al.
    An investigation into biomarkers for the diagnosis of ABPA and aspergillus disease in cystic fibrosis. Pediatr Pulmonol 2019; 54: 1787–1793. doi:10.1002/ppul.24465
    OpenUrl
  5. ↵
    1. Quanjer PH,
    2. Stanojevic S,
    3. Cole TJ, et al.
    Multi-ethnic reference values for spirometry for the 3–95-yr age range: the global lung function 2012 equations. Eur Respir J 2012; 40: 1324–1343. doi:10.1183/09031936.00080312
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Brusasco V,
    2. Crapo R,
    3. Viegi G, et al.
    Coming together: the ATS/ERS consensus on clinical pulmonary function testing. Eur Respir J 2005; 26: 1–2. doi:10.1183/09031936.05.00034205
    OpenUrlFREE Full Text
  7. ↵
    1. Levine H,
    2. Cohen-Cymberknoh M,
    3. Klein N, et al.
    Reversible airway obstruction in cystic fibrosis: common, but not associated with characteristics of asthma. J Cyst Fibros 2016; 15: 652–659. doi:10.1016/j.jcf.2016.01.003
    OpenUrl
  8. ↵
    1. Pollak M,
    2. Wilson D,
    3. Klingel M, et al.
    Bronchodilator response in children with cystic fibrosis pulmonary exacerbations. Am J Respir Crit Care Med 2019; 199: A5682. doi:10.1164/ajrccm-conference.2019.199.1_MeetingAbstracts.A5682
    OpenUrl
  9. ↵
    1. Marshall B,
    2. Faro A,
    3. Elbert A, et al.
    Cystic Fibrosis Foundation Patient Registry 2018, Annual Data Report. Bethesda, Cystic Fibrosis Foundation, 2018.
PreviousNext
Back to top
View this article with LENS
Vol 56 Issue 2 Table of Contents
European Respiratory Journal: 56 (2)
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Bronchodilator responsiveness in children with cystic fibrosis and allergic bronchopulmonary aspergillosis
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
Bronchodilator responsiveness in children with cystic fibrosis and allergic bronchopulmonary aspergillosis
Mordechai Pollak, Michelle Shaw, David Wilson, Hartmut Grasemann, Felix Ratjen
European Respiratory Journal Aug 2020, 56 (2) 2000175; DOI: 10.1183/13993003.00175-2020

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Bronchodilator responsiveness in children with cystic fibrosis and allergic bronchopulmonary aspergillosis
Mordechai Pollak, Michelle Shaw, David Wilson, Hartmut Grasemann, Felix Ratjen
European Respiratory Journal Aug 2020, 56 (2) 2000175; DOI: 10.1183/13993003.00175-2020
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • Shareable PDF
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

Agora

  • Airway immune responses to COVID-19 vaccination in COPD patients
  • Wider access to rifapentine-based regimens is needed for TB care globally
  • Association between immunosuppressants and outcomes of COVID-19
Show more Agora

Research letters

  • Airway immune responses to COVID-19 vaccination in COPD patients
  • Wider access to rifapentine-based regimens is needed for TB care globally
  • Association between immunosuppressants and outcomes of COVID-19
Show more Research letters

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2023 by the European Respiratory Society