sensitized subjects. Allergists thus need to be aware of
such potential allergens to which patients may be exposed
in routine medical procedures.
Maho Suzukawa, MDa
Masao Yamaguchi, MD, PhDa
Akiko Komiya, MD, PhDa
Miwako Kimura, MDb
Takaharu Nito, MDb
Kazuhiko Yamamoto, MD, PhDa
Fromathe Department of Allergy and Rheumatology andbthe Department
of Otolaryngology, University of Tokyo Graduate School of Medicine,
Disclosure of potential conflict of interest: The authors have declared they
have no conflict of interest.
1. Alvarado CJ, Reichelderfer M. APIC guideline for infection prevention
and control in flexible endoscopy. Association for Professionals in Infec-
tion Control. Am J Infect Control 2000;28:138-55.
2. Cooke RP, Goddard SV, Whymant-Morris A, Sherwood J, Chatterly R.
An evaluation of Cidex OPA (0.55% ortho-phthalaldehyde) as an alter-
native to 2% glutaraldehyde for high-level disinfection of endoscopes.
J Hosp Infect 2003;54:226-31.
3. Calder IM, Wright LP, Grimstone D. Glutaraldehyde allergy in endoscopy
units. Lancet 1992;339:433.
4. Sokol WN. Nine episodes of anaphylaxis following cystoscopy caused by
Cidex OPA (ortho-phthalaldehyde) high-level disinfectant in 4 patients
after cystoscopy. J Allergy Clin Immunol 2004;114:392-7.
Available online March 31, 2006.
Obesity and airway inflammation in asthma
To the Editor:
The concurrent increase in the prevalence of obesity
and asthma leads to the interest in potential mechanisms
linking these2 epidemics.1Obesity hasbeen recentlysug-
gested as a proinflammatory state,2but the links with
airway inflammation are still scarce. Our study aimed to
investigate the association between overweight or obesity
inflammation assessed by exhaled nitric oxide (FENO), a
simple, quick, noninvasive, and highly reproducible sur-
rogate marker of airway inflammation that could enhance
diagnosis and management of asthma.
After informed consent, 297 nonsmoking patients, age
15 to 73 years, with a medical diagnosis of asthma were
recruited from an asthma and allergy outpatient clinic at
University Central Hospital in Porto. The study protocol
included FENOmeasurement using the online technique
with the NIOX system (Aerocrine, Stockholm, Sweden)3;
FEV1determination using PIKO-1 (Ferraris Respiratory,
Hertford, United Kingdom)4; and body weight and height
with stadiometer (Seca model 700; Seca, Hamburg, Ger-
many) followed by BMI determination (weight/height2).
The World Health Organization BMI Classification was
used to define underweight (<18.5 kg/m2), normal weight
(18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and
obesity (?30.0 kg/m2).5Atopy, defined by skin prick
test to common aeroallergens, and inhaled corticosteroid
use were registered. The data analysis was performed by
using the statistical package SPSS, 12.0 version (SPSS
Inc, Chicago, Ill). FENOwas logarithmically transformed
to attain normal distribution. Spearman correlation, linear
the association between BMIandFENOandthe effect after
adjusting for age, FEV1, sex, atopy, and inhaled cortico-
steroid use. A .05 level of significance and 95% CIs were
226) were female, 55% were atopic, and the mean (SD)
percent predicted FEV1was 85.7 (20.5). Geometric mean
(95% CI) of FENOwas 30.6 (27.9-33.6) and of BMI was
38% were overweight, 40% were normal, and 2% under-
weight. Spearman correlation and linear regression analy-
sis showed a negative association between mean BMI and
noted between overweight or obese patients with asthma
with the others. In normal weight/underweight patients
with asthma, no association between BMI and FENO
(rs5 20.061, P 5 .499; B 5 0.019; 95% CI, 20.039 to
0.077; P 5 .511) was found. In overweight or obese
patients with asthma, a significant negative association
with FENO(rs5 20.307, P < .001; B 5 20.049; 95%
CI, 20.075 to 20.023; P < .001) was observed (Fig 1).
By general linear model analysis, BMI maintained the
negative association with FENO(B 5 20.032, 95% CI,
for age, FEV1, sex, atopy, and inhaled corticosteroid use.
(B 5 20.014; 95% CI, 20.020 to 20.008; F 5 18.10,
P < .001). In overweight or obese patients with asthma,
BMI (B 5 20.047, 95% CI, 20.077 to 20.017; F 5
9.38, P 5 .003) and age (B 5 20.013, 95% CI, 20.022
to 20.003; F 5 6.23, P 5 .014) maintained a significant
FIG 1. Association between BMI (kg/m2) and FENO(ppb) in patients
with asthma. (.) Normal/underweight regression line (R25 0.004);
(_ _) overweight/obese regression line (R25 0.074); (__) all patients
regression line (R25 0.094). (s) Normal/underweight patients with
asthma; (C) overweight/obese patients with asthma. LnFENO, FENO
J ALLERGY CLIN IMMUNOL
VOLUME 117, NUMBER 6
Letters to the Editor 1501
Letters to the Editor
negative association with FENO. In normal weight/ Download full-text
underweight patients with asthma, only age affected
FENO (B 5 20.017, 95% CI, 20.026 to 20.008;
F 5 13.89, P < .001).
We observed a negative association between BMI and
FENOin overweight or obese patients with asthma, inde-
pendent from sex, atopy, lung function, or corticosteroid
use. Despite the adjusting to these main confounders, we
cannot exclude the hypotheses that FENOmeasurement
could be affected by others factors that cannot have been
Several cross-sectional and case-control studies have
found obesity to be associated with asthma diagnosis,
respiratory symptoms, poor lung function, and increased
airway hyperreactivity. Plausible links between asthma
and obesity include mechanical factors, inflammatory
conditions, and stress models. The increased abdominal
and chest wall mass causes decreased functional residual
capacity and reduced lung and tidal volumes.6,7Obesity is
also a state of chronic and low-grade systemic inflamma-
tion with increased levels of the proinflammatory leptin
and plasminogen activator inhibitor and decreased serum
levels of the protective anti-inflammatory adiponectin.3
ing evidence. In children, BMI had no association with
FENO,8-10whereas in 24 nonobese adults without asthma,
a positive association has been reported.11Recently, a
case-control study described a positive association in nor-
mal weight and obese healthy adults, but no significant
association was observed in the asthma group. Although
BMI was correlated with serum leptin levels in both
groups, FENOwas not related to serum leptin levels in
patients with asthma.12
Our findings are based on cross-sectional data, and
a causal relationship cannot be inferred. Although BMI
is not the gold standard to assess body composition, it
correlates with total body fat content and has been the
most widely used measure to assess overweight or obesity
and to monitor changes in body weight. In the future,
research should include more complex anthropometric
measures (eg, waist-circumference, skinfold thickness, or
bioelectrical impedance analysis) that assess total body
mass distribution, including body fat mass measure.
In conclusion, the observed negative association be-
tween BMI and FENOin overweight or obese patients with
asthma provides additional support to the hypothesized
mechanical link between obesity and asthma.
Renata Barros, MSca,b
Andre ´ Moreira, MDb,d
Joa ˜o Fonseca, MDb,e
Pedro Moreira, PhDa
Lia Fernandes, MD, PhDc,f
Jose ´ Ferraz de Oliveira, MDb
Luı ´s Delgado, MD, PhDb,d
M. Grac xa Castel-Branco, MDb
Fromathe Faculty of Nutrition and Food Sciences, University of Porto; and
bImmunoallergology andcPsychiatry, Hospital of S. Joa ˜o; anddImmunol-
ogy,eBiostatistical and Medical Informatics, andfPsychiatry, Faculty of
Medicine, University of Porto, Porto, Portugal.
Disclosure of potential conflict of interest: The authors have declared that they
have no conflict of interest.
1. Ford ES. The epidemiology of obesity and asthma. J Allergy Clin Immu-
2. Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin
3. Recommendations for standardized procedures for the on-line and off-
line measurement of exhaled lower respiratory nitric oxide and nasal
nitric oxide in adults and children—1999. This official statement of
the American Thoracic Society was adopted by the ATS Board of Direc-
tors, July 1999. Am J Respir Crit Care Med 1999;160:2104-17.
4. Fonseca JA, Costa-Pereira A, Delgado L, Silva LN, Magalha ˜es M,
Castel-Branco MG, et al. Pulmonary function electronic monitoring
devices: a randomized agreement study. Chest 2005;128:1258-65.
5. World Health Organization. Obesity: preventing and managing the
global epidemic. WHO Technical Report Series No. 894. Geneva,
Switzerland: WHO; 2000.
6. Shore SA, Fredberg JJ. Obesity, smooth muscle and airway hyperrespon-
siveness. J Allergy Clin Immunol 2005;115:925-7.
7. King GG, Brown NJ, Diba C, Thorpe CW, Munoz P, Marks GB, et al.
The effects of body weight on airway calibre. Eur Respir J 2005;25:
8. Leung TF, Li CY, Lam CW, Au CS, Yung E, Chan IH, et al. The relation
between obesity and asthmatic airway inflammation. Pediatr Allergy
9. Buchvald F, Baraldi E, Carraro S, Gaston B, De Jongste J, Pijnenburg
MWH, et al. Measurements of exhaled nitric oxide in healthy subjects
age 4 to 17 years. J Allergy Clin Immunol 2005;115:1130-6.
10. Wong GW, Liu EK, Leung TF, Yung E, Ko FW, Hui DS, et al. High
levels and gender difference of exhaled nitric oxide in Chinese school-
children. Clin Exp Allergy 2005;35:889-93.
11. De Winter-de Groot KM, Van der Ent CK, Prins I, Tersmette JM, Uiter-
waal CS. Exhaled nitric oxide: the missing link between asthma and
obesity? J Allergy Clin Immunol 2005;115:419-20.
12. Kazaks A, Uriu-Adams JY, Stern JS, Albertson TE. No significant rela-
tionship between exhaled nitric oxide and body mass index in people
with asthma. J Allergy Clin Immunol 2005;116:929-30; author reply
Available online May 2, 2006.
Eosinophil b1integrin activation state
correlates with asthma activity in a blind
study of inhaled corticosteroid withdrawal
To the Editor:
Eosinophilic inflammation is a characteristic feature of
asthma regulated by many factors, including treatment
with corticosteroids.1On gradual inhaled corticosteroid
(ICS) reduction,thereisanincreasein sputumeosinophils
that often precedes changes in airway caliber and loss of
asthma control.2,3Conversely, ICS treatment directed to-
ward a reduction in sputum eosinophils improves asthma
control and prevents exacerbations.4These and other re-
ports suggest that eosinophils in the airway are associated
with diminished asthma control and increased risk for ex-
acerbation and that eosinophil recruitment to the airway
mation and exacerbation.
Eosinophil recruitment to the airway involves integrins
and their ligands.5a4b1Integrin mediates blood eosino-
phil adhesion to vascular cell adhesion molecule 1, pre-
ferentially induced on endothelium in response to TH2
J ALLERGY CLIN IMMUNOL
1502 Letters to the Editor
Letters to the Editor