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Rose-Marie A. Mackay, PhD; Christopher L. Grainge, MD, PhD; Laurie C. Lau, PhD; Clair Barber, BSc; Howard W. Clark, MD, PhD; Peter H. Howarth, MD, DM
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: See earlier cited article for author conflicts of interest.

aClinical and Experimental Sciences University of Southampton and Southampton General Hospital, Southampton, England

bDepartment of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia

cSouthampton NIHR Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, England

CORRESPONDENCE TO: Rose-Marie Mackay, PhD, University of Southampton, Faculty of Medicine, Department of Child Health, Southampton General Hospital, Tremona Rd, Southampton SO16 7YD, UK


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(2):474. doi:10.1016/j.chest.2016.05.033
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We thank Dr Benfante et al for their letter. We are delighted that they have been able to replicate our findings reported in CHEST and add to our data that serum surfactant protein D (SP-D) is elevated in severe asthma and as such may act as a biomarker of small airway events. This was indicated by our identification of reduced concentrations of SP-D in BAL, which has implications for small airway function and innate immune defense. Benfante et al questioned our statement that “To the best of our knowledge, this study is the first to investigate the relationship between asthma and SP-D concentration in patients with such severe disease.” They respectfully disagree with our statement, referring to their recent report that serum SP-D concentrations are significantly higher in patients with severe asthma as opposed to healthy control subjects and individuals with mild asthma and that their levels correlate with the degree of airflow obstruction. However, our CHEST publication, first available as an e-publication in January 2016, predated their e-publication in March 2016, and as such our statement is correct. However, this is not of scientific importance; we highlight this only to provide the correct information and make the record clear. Of more importance is their validation of our findings and considerations about future work to understand the implications and the value of serum SP-D as a biomarker to potentially monitor the impact of therapy on the distal airways. This correspondence brings together similar research at separate sites and highlights the need for further research to investigate possible mechanisms of airway SP-D deficiency in severe asthma. As such, we welcome possible collaborations into understanding the underlying causes. A recent review has highlighted several important areas of further investigation, for example, are the low levels in the airway a result of consumption or cleavage associated with increased airway infection? We recognize that the airways are not sterile and that there is an altered colonization in severe asthma. We have recently reported that some bacterial strains may shield core structures in the lipopolysaccharide, which are targets for SP-D binding by the carbohydrate recognition domain; proteases present in severe asthma may cleave SP-D within the carbohydrate recognition domain and inhibit these innate immune defense functions, contributing to ongoing inflammation and low SP-D levels in the BAL.

References

Mackay R.M. .Grainge C.L. .Lau L.C. .et al Airway surfactant protein D deficiency in adults with severe asthma. Chest. 2016;149:1165-1172 [PubMed]journal. [CrossRef] [PubMed]
 
Benfante A. .Battaglia S. .Principe S. .et al Asthmatics with high levels of serum surfactant protein D have more severe disease. Eur Respir J. 2016;47:1864-1867 [PubMed]journal. [CrossRef] [PubMed]
 
Mitchell P.D. .O'Byrne P.M. . Surfactant protein-D and asthma. Chest. 2016;149:1121-1122 [PubMed]journal. [CrossRef] [PubMed]
 
Green B.J. .Wiriyachaiporn S. .Grainge C. .et al Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma. PloS One. 2014;9:e100645- [PubMed]journal. [CrossRef] [PubMed]
 
Clark H.W. .Mackay R.M. .Deadman M.E. .et al Crystal structure of a complex of surfactant protein D (SP-D) and Haemophilus influenzae lipopolysaccharide reveals shielding of core structures in SP-D-resistant strains. Infect Immun. 2016;84:1585-1592 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Mackay R.M. .Grainge C.L. .Lau L.C. .et al Airway surfactant protein D deficiency in adults with severe asthma. Chest. 2016;149:1165-1172 [PubMed]journal. [CrossRef] [PubMed]
 
Benfante A. .Battaglia S. .Principe S. .et al Asthmatics with high levels of serum surfactant protein D have more severe disease. Eur Respir J. 2016;47:1864-1867 [PubMed]journal. [CrossRef] [PubMed]
 
Mitchell P.D. .O'Byrne P.M. . Surfactant protein-D and asthma. Chest. 2016;149:1121-1122 [PubMed]journal. [CrossRef] [PubMed]
 
Green B.J. .Wiriyachaiporn S. .Grainge C. .et al Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma. PloS One. 2014;9:e100645- [PubMed]journal. [CrossRef] [PubMed]
 
Clark H.W. .Mackay R.M. .Deadman M.E. .et al Crystal structure of a complex of surfactant protein D (SP-D) and Haemophilus influenzae lipopolysaccharide reveals shielding of core structures in SP-D-resistant strains. Infect Immun. 2016;84:1585-1592 [PubMed]journal. [CrossRef] [PubMed]
 
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