pneumonia has been also commented upon by other experts in
the field [5, 6]. Thus, the present authors believe that the
prophylactic administration of antimicrobials via the respira-
tory tract for ventilator-associated pneumonia deserves the
attention of investigators. However, future studies should
focus not only on the effectiveness of this strategy but also on
safety and the issue of emergence of antimicrobial resistance.
M.E. Falagas*,#," and I.I. Siempos*
*Alfa Institute of Biomedical Sciences, and "Dept of Medicine,
Henry Dunant Hospital, Athens, Greece. #Dept of Medicine,
Tufts University School of Medicine, Boston, MA, USA.
STATEMENT OF INTEREST
None declared.
REFERENCES
1 Lorente L, Blot S, Rello J. Evidence on measures for the
prevention of ventilator-associated pneumonia. Eur Respir J
2007; 30: 1193–1207.
2 Dodek P, Keenan S, Cook D, et al. Evidence-based clinical
practice guideline for the prevention of ventilator-associated
pneumonia. Ann Intern Med 2004; 141: 305–313.
3 Falagas ME, Siempos II, Bliziotis IA, Michalopoulos A.
Administration of antibiotics via the respiratory tract for the
prevention of ICU-acquired pneumonia: a meta-analysis of
comparative trials. Crit Care 2006; 10: R123.
4 Claridge JA, Edwards NM, Swanson J, et al. Aerosolized
ceftazidime prophylaxis against ventilator-associated pneu-
monia in high-risk trauma patients: results of a double-blind
randomized study. Surg Infect (Larchmt) 2007; 8: 83–90.
5 MacIntyre NR, Rubin BK. Respiratory therapies in the
critical care setting. Should aerosolized antibiotics be
administered to prevent or treat ventilator-associated
pneumonia in patients who do not have cystic fibrosis?
Respir Care 2007; 52: 416–421.
6 Dhand R. The role of aerosolized antimicrobials in the
treatment of ventilator-associated pneumonia. Respir Care
2007; 52: 866–884.
DOI: 10.1183/09031936.00172707
Competitive swimmers with allergic asthma show a
mixed type of airway inflammation
To the Editors:
Elite swimmers are at increased risk of asthma [1]. This has
been attributed to airway inflammation and increased airway
responsiveness induced by high-intensity long-term exercise
and repeated exposure to the chlorine-rich atmosphere in
swimming pools during training and competition [2, 3].
Recently, increased levels of leukotriene (LT)B4 in exhaled
breath condensate and normal exhaled nitric oxide fraction
(FeNO) levels have been reported in five elite swimmers,
suggesting possible underlying neutrophilic airway inflamma-
tion [4]. Previous analysis of induced sputum in nonasthmatic
elite swimmers showed increased proportion of eosinophils
and neutrophils compared with healthy controls [3].
We aimed to characterise the airway inflammation in
competitive asthmatic swimmers. Athletes from the FC Porto
main swimming team and 20 nonathlete asthmatics were
recruited; participants gave informed consent. Subjects were
classified by their asthma and training status as asthmatic
swimmers (n56, two female, aged 17¡2 yrs, competing
8¡3 yrs, training 16¡4 h?week-1), asthmatics (n520, eight
female, aged 14¡3 yrs) and swimmers (n520, six female, aged
17¡2 yrs, competing 8¡3 yrs, training 17¡3 h?week-1).
All asthmatics and nine (45%) of the swimmers were atopic
according to skin-prick test results. None smoked. During two
visits to the clinic, 1 week apart, subjects’ sputum cell counts,
FeNO, lung volumes and airway responsiveness to methacholine
(provocative dose causing a 20% fall in forced expiratory
volume in one second (FEV1); PD20) were determined. Sputum
cell counts were further compared with reference values from a
group of healthy schoolchildren (n515, five female, aged
9¡2 yrs, 40% atopic) [5].
Sputum was examined as described previously [3]. Briefly,
after induction using an inhalation of hypertonic saline,
sputum was selected and treated with dithiothreitol
(Sputolysin1; Calbiochem Corporation, San Diego, CA, USA).
The suspension was centrifuged and the cell pellet was
resuspended. Cytospins were prepared and stained using
May-Gru¨nwald/Giemsa. Differential cell counts were made by
counting a minimum of 500 nonsquamous cells. FeNO was
measured by chemiluminescence (NIOX; Aerocrine,
Stockholm, Sweden) and PD20 methacholine was determined
using the dosimeter method, according to recommendations [6,
7]. ANOVA was used to detect differences between groups.
Due to the skewed distribution, eosinophil counts and PD20
methacholine comparisons were made after logarithmic
transformation. In order to permit analysis in the log scale, a
constant (0.01) was added to each value to eliminate 0 values.
A p-value ,0.05 was considered to be stastically significant.
Induced sputum samples of asthmatic swimmers showed
increased numbers of eosinophils and neutrophils compared
with both healthy subjects and asthmatic patients respectively,
and lymphocytes compared with healthy subjects, although
the numbers were approximately the same as in swimmers or c
EUROPEAN RESPIRATORY JOURNAL VOLUME 31 NUMBER 5 1139

asthmatic patients. Asthmatic swimmers had a similar magni-
tude of FeNO but significantly more pronounced airway
responsiveness than asthmatics (fig. 1).
Features of asthma in competitive swimmers seem to be the
result of mixed type effects. Although the cross-sectional
nature of our study does not allow us to establish causal
relationships, allergic inflammation results in sputum eosino-
philia and increased FeNO, while sputum neutrophils may
result from the daily exposure of the pool training environ-
ment. Increased bronchial responsiveness and lymphocyte
numbers could be the result of both processes as they occurred
similarly in swimmers and asthmatics.
Two factors could contribute to the neutrophilic airway
inflammation in asthmatic competitive swimmers. First,
endurance exercise associated hyperventilation and the inhala-
tion of hypotonic aerosolised droplets from the pool surface
during training may cause epithelial damage [1] and sub-
sequent inflammation. Secondly, chronic low-grade exposure
to chlorine derivatives may be related to the observed
increased levels of exhaled LTB4 in elite swimmers [4]. This
observation is also supported by the findings in children
accidentally exposed to chlorine, with development of respira-
tory symptoms, lung function impairment and exhaled breath
alterations, represented mainly by an increase in LTs and a
decrease in FeNO [8]. If this is the case, new therapeutic
approaches that, in addition to inhaled corticosteroids, would
target the 5-lipoxygenase pathway could have a role attenuat-
ing the neutrophilic airway inflammation in swimmers
with asthma.
In conclusion, asthma in allergic competitive swimmers is
characterised by mixed type of eosinophilic and neutrophilic
inflammation, which increase normal exhaled nitric oxide
fraction and cause airway hyperresponsiveness. Daily expo-
sure to aerosolised water droplets and chlorine derivatives
probably contribute to the neutrophilic inflammation, which
might respond poorly to standard asthma medication.
A. Moreira*,#, L. Delgado*,#, C. Palmares*, C. Lopes*,#,
T. Jacinto#, P. Rytila¨", J.A. Silva+, M.G. Castel-Branco# and
T. Haahtela"
*Dept of Immunology, Faculty of Medicine, University of
Porto, #Immuno-allergology, Hospital of Sa˜o Joa˜o, and +FC
Porto Swimming Section, Porto, Portugal. "Skin and Allergy
Hospital, Helsinki University Central Hospital, Helsinki,
Finland.
STATEMENT OF INTEREST
A statement of interest for this manuscript can be found at
www.erj.ersjournals.com/misc/statements.shtml
ACKNOWLEDGEMENTS
The present authors would like to thank all subjects for their
participation and the technical and administrative staff of FC
Porto Swimming Section for logistical help. They would also
like to thank S. Simo˜es (Dept of Immunology, Faculty of
Medicine, University of Porto, Porto, Portugal) for help with















































































































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FIGURE 1. Per cent sputum a) eosinophils, c) neutrophils and e) lymphocytes
and b) exhaled nitric oxide (FeNO) ppb, d) airway responsiveness provocative dose
of methacholine causing a 20% fall in forced expiratory volume in one second (PD20
methacholine) and f) lung function (% predicted forced expiratory volume in one
second (FEV1)) in competitive asthmatic swimmers (study subjects) compared with
asthmatic subjects, competitive swimmers and healthy subjects (controls). Boxes
represent mean and whiskers represent confidence intervals. #: p50.015; +:
p50.002; ": p50.005; 1: p50.001; *: p,0.05; ***: p,0.001.
SUPPORT STATEMENT
A. Moreira holds a Grant from the Finnish Centre for
International Mobility and a Fellowship Award from the
European Academy of Allergy and Clinical Immunology.
1140 VOLUME 31 NUMBER 5 EUROPEAN RESPIRATORY JOURNAL

data collection and J. Fonseca (Biostatistics and Medical
Informatics, Faculty of Medicine, University of Porto and
Immuno-allergology, Hospital of Sa˜o Joa˜o, Porto, Portugal) for
manuscript revision.
REFERENCES
1 Helenius I, Haahtela T. Allergy and asthma in elite summer
sport athletes. J Allergy Clin Immunol 2000; 106: 444–452.
2 Helenius IJ, Tikkanen HO, Sarna S, Haahtela T. Asthma and
increased bronchial responsiveness in elite athletes: atopy
and sport event as risk factors. J Allergy Clin Immunol 1998;
101: 646–652.
3 Helenius IJ, Rytila¨ P, Metso T, Haahtela T, Venge P,
Tikkanen HO. Respiratory symptoms, bronchial responsive-
ness, and cellular characteristics of induced sputum in elite
swimmers. Allergy 1998; 53: 346–352.
4 Piacentini GL, Rigotti E, Bodini A, Peroni D, Boner AL.
Airway inflammation in elite swimmers. J Allergy Clin
Immunol 2007; 119: 1559–1560.
5 Rytila¨ P, Pelkonen AS, Metso T, Nikander K, Haahtela T,
Turpeinen M. Induced sputum in children with newly
diagnosed mild asthma: the effect of 6 months of treatment
with budesonide or disodium cromoglycate. Allergy 2004;
59: 839–844.
6 American Thoracic Society, European Respiratory Society.
ATS/ERS recommendations for standardized procedures
for the online and offline measurement of exhaled lower
respiratory nitric oxide and nasal nitric oxide, 2005. Am J
Respir Crit Care Med 2005; 171: 912–930.
7 Sterk PJ, Fabbri LM, Quanjer PhH, et al. Airway responsive-
ness. Standardized challenge testing with pharmacological,
physical and sensitizing stimuli in adults. Report Working
Party Standardization of Lung Function Tests, European
Community for Steel and Coal. Official Statement of the
European Respiratory Society. Eur Respir J 1993; 6: Suppl. 16,
53–83.
8 Bonetto G, Corradi M, Carraro S, et al. Longitudinal
monitoring of lung injury in children after acute chlorine
exposure in a swimming pool. Am J Respir Crit Care Med
2006; 174: 545–549.
DOI: 10.1183/09031936.00175207
Idiopathic pulmonary fibrosis and nonspecific
interstitial pneumonia should stay separate
To the Editors:
We read with interest the recent perspective by MAHER et al.
[1], challenging the current definition of idiopathic pulmonary
fibrosis (IPF). Questioning dogma is critical to progress in
science and the authors should be commended for doing so.
We agree that the relationship between disease entity (i.e.
clinical diagnosis) and histopathological pattern is more
complex than simply equating IPF with usual interstitial
pneumonia (UIP), and that distinguishing idiopathic UIP from
idiopathic nonspecific interstitial pneumonia (NSIP) can some-
times be difficult, even for expert clinicians, radiologists and
pathologists [2]. Indeed, the American Thoracic Society/
European Respiratory Society Consensus Statement made
these points quite deliberately [3].
However, we disagree with the authors’ contention that
‘‘idiopathic UIP and idiopathic NSIP, sharing a common
clinical phenotype, form a spectrum of disease with a common
pathogenesis’’ [1]. This blanket statement assumes a homo-
geneity to idiopathic NSIP and idiopathic UIP that is contrary
to the evidence. The idea of a distinct clinical phenotype for
idiopathic NSIP is supported by demographic, serological and
survival differences seen when IPF and idiopathic NSIP
patients are compared [4–6], and by the differences, not
similarities, seen in gene expression profiles (six of 10
published NSIP profiles are distinct from UIP while four are
similar) [7, 8].
It is our belief that idiopathic nonspecific interstitial pneumo-
nia represents a collection of conditions including occult
connective tissue disease, hypersensitivity pneumonia and,
perhaps, truly idiopathic cases, and should not be lumped
together clinically with idiopathic pulmonary fibrosis. We
share the hope of MAHER et al. [1] that new and emerging
methods of categorising disease will allow us to better
understand the relationship of histopathology to pathogenesis
and to refine future definitions and diagnostic criteria.
H.R. Collard and T.E. King Jr
Dept of Medicine, University of California, San Francisco, CA,
USA.
STATEMENT OF INTEREST
None declared.
REFERENCES
1 Maher TM, Wells AU, Laurent GJ. Idiopathic pulmonary
fibrosis: multiple causes and multiple mechanisms? Eur
Respir J 2007; 30: 835–839.
2 Flaherty KR, King TE Jr, Raghu G, et al. Idiopathic interstitial
pneumonia: what is the effect of a multidisciplinary
approach to diagnosis? Am J Respir Crit Care Med 2004;
170: 904–910. c
EUROPEAN RESPIRATORY JOURNAL VOLUME 31 NUMBER 5 1141