Author's response to Persson letter
===================================

* Sally Wenzel

*   Not Applicable

Dr Persson raises excellent points regarding the potential for epithelial cells to contribute to the clearance of eosinophils from tissue. We are in agreement that eosinophils can migrate from bone marrow to blood to submucosa to epithelium to lumen. However, the speed of the process, the role and response of each compartment, the stimulus for it and its overall control remain poorly understood. Dr Persson suggests that previous reports show an inverse relationship of tissue compared with luminal/epithelial eosinophils following allergen challenge such that the accumulation of eosinophils in the lumen equates to resolution of inflammation. This suggests to him that the epithelium plays a resolving role.1,2 We agree that at certain timepoints following an acute stimulus, this relationship may exist. However, chronic asthma represents a more dynamic and ongoing process, with the level of control and severity related to the intensity and chronicity of the cellular migration. In fact, unlike the allergen challenge studies alluded to, the relation of submucosal to epithelial/luminal eosinophils is almost always positive.3 But importantly, perhaps because sputum samples are an integration of multiple airway samples over time and not a tiny (often <1 mm3) static piece of tissue, there are consistently stronger relationships of asthma severity and control to sputum/luminal eosinophils than to those in tissue especially in those patients treated with inhaled steroids (3 and personal unpublished data).

Thus, in contrast to Dr Persson's assertion, the finding of luminal eosinophils does not appear to relate to resolution of inflammation, rather to uncontrolled disease, which requires and responds to treatment with increased anti-inflammatory therapies.4 The ongoing expression of epithelial eotaxin-2 and eotaxin-3, their relation to sputum eosinophils, and importantly to severe poorly controlled asthma observed in our recent study, implies that this migration initiates a process associated with luminal migration, and with epithelial damage as well.5 In fact, this is consistent with multiple studies that report a deleterious effect of eosinophils and their products on epithelial function.6 ,7 

Although definitive evidence that epithelial and luminal eosinophils have negative rather than positive effects in chronic asthma requires inhibition of epithelial migration through inhaled CCR3 antagonists, we believe that the bulk of the data support a negative impact of epithelial-eosinophil migration on asthma control.

## Acknowledgments

We thank Dr Persson for his comments on our paper.

## Footnotes

*   Funding None.

*   Competing interests None.

*   Provenance and peer review Commissioned; internally peer reviewed.

## References

1.  Persson C, Uller L. Transepithelial exit of leucocytes: inflicting, reflecting or resolving airway inflammation? Thorax 2010;65:1111–5.
    
    [Abstract/FREE Full Text](http://thorax.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToidGhvcmF4am5sIjtzOjU6InJlc2lkIjtzOjEwOiI2NS8xMi8xMTExIjtzOjQ6ImF0b20iO3M6MjQ6Ii90aG9yYXhqbmwvNjgvMi8xODkuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

2.  Erjefält JS, Korsgren M, Nilsson MC, et al. Association between inflammation and epithelial damage-restitution processes in allergic airways in vivo. Clin Exp Allergy 1997;27:1344–55.
    
    [CrossRef](http://thorax.bmj.com/lookup/external-ref?access_num=10.1111/j.1365-2222.1997.tb01181.x&link_type=DOI) 
    
    [PubMed](http://thorax.bmj.com/lookup/external-ref?access_num=9420140&link_type=MED&atom=%2Fthoraxjnl%2F68%2F2%2F189.atom) 
    
    [Web of Science](http://thorax.bmj.com/lookup/external-ref?access_num=A1997YK49300018&link_type=ISI) 

3.  Lemière C, Ernst P, Olivenstein R, et al. Airway inflammation assessed by invasive and noninvasive means in severe asthma: eosinophilic and noneosinophilic phenotypes. J Allergy Clin Immunol 2006;118:1033–9.
    
    [CrossRef](http://thorax.bmj.com/lookup/external-ref?access_num=10.1016/j.jaci.2006.08.003&link_type=DOI) 
    
    [PubMed](http://thorax.bmj.com/lookup/external-ref?access_num=17088126&link_type=MED&atom=%2Fthoraxjnl%2F68%2F2%2F189.atom) 
    
    [Web of Science](http://thorax.bmj.com/lookup/external-ref?access_num=000244282300006&link_type=ISI) 

4.  Green RH, Brightling CE, McKenna S, et al. Asthma exacerbations and sputum eosinophil counts: a randomisedcontrolled trial. Lancet 2002;360:1715–21.
    
    [CrossRef](http://thorax.bmj.com/lookup/external-ref?access_num=10.1016/S0140-6736(02)11679-5&link_type=DOI) 
    
    [PubMed](http://thorax.bmj.com/lookup/external-ref?access_num=12480423&link_type=MED&atom=%2Fthoraxjnl%2F68%2F2%2F189.atom) 
    
    [Web of Science](http://thorax.bmj.com/lookup/external-ref?access_num=000179636800007&link_type=ISI) 

5.  Coleman JM, Naik C, Holguin F, et al. Epithelial eotaxin-2 and eotaxin-3 expression: relation to asthma severity, luminal eosinophilia and age at onset. Thorax 2012;67:1061–66.
    
    [Abstract/FREE Full Text](http://thorax.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToidGhvcmF4am5sIjtzOjU6InJlc2lkIjtzOjEwOiI2Ny8xMi8xMDYxIjtzOjQ6ImF0b20iO3M6MjQ6Ii90aG9yYXhqbmwvNjgvMi8xODkuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

6.  Pégorier S, Wagner LA, Gleich GJ, et al. Eosinophil-derived cationic proteins activate the synthesis of remodeling factors by airway epithelial cells. J Immunol 2006;177:4861–9.
    
    [Abstract/FREE Full Text](http://thorax.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiamltbXVub2wiO3M6NToicmVzaWQiO3M6MTA6IjE3Ny83LzQ4NjEiO3M6NDoiYXRvbSI7czoyNDoiL3Rob3JheGpubC82OC8yLzE4OS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

7.  Khoo SG, Al-Alawi M, Walsh MT, et al. Eosinophil peroxidase induces the expression and function of acid-sensing ionchannel-3 in allergic rhinitis: in vitro evidence in cultured epithelial cells. Clin Exp Allergy 2012;42:1028–39.
    
    [CrossRef](http://thorax.bmj.com/lookup/external-ref?access_num=10.1111/j.1365-2222.2012.03980.x&link_type=DOI) 
    
    [PubMed](http://thorax.bmj.com/lookup/external-ref?access_num=22702502&link_type=MED&atom=%2Fthoraxjnl%2F68%2F2%2F189.atom)