The post Pulmonary Function In Children appeared first on Contact Numbers.
]]>Rita Mattiello, Javier Mallol, Gilberto Bueno Fischer,
Helena Teresinha Mocelin, Belkys Rueda, Edgar Enrique Sarria
Objective: To describe the pulmonary function in children and adolescents with postinfectious bronchiolitis obliterans (PIBO), as well as to evaluate potential risk factors for severe impairment of pulmonary function. Methods: The pulmonary function of 77 participants, aged 8-18 years, was assessed by spirometry and plethysmography. The following parameters were analyzed: FVC; FEV1; FEF25-75%; FEV1/FVC; RV; TLC; RV/TLC; intrathoracic gas volume; and specific airway resistance (sRaw). We used Poisson regression to investigate the following potential risk factors for severe impairment of pulmonary function: gender; age at first wheeze; age at diagnosis; family history of asthma; tobacco smoke exposure; length of hospital stay; and duration of mechanical ventilation. Results: The mean age was 13.5 years. There were pronounced decreases in FEV1 and FEF25-75%, as well as increases in RV and sRaw. These alterations are characteristic of obstructive airway disease. For the parameters that were the most affected, the mean values (percentage of predicted) were as follows: FEV1 = 45.9%; FEF25-75% = 21.5%; RV = 281.1%; RV/TLC = 236.2%; and sRaw = 665.3%. None of the potential risk factors studied showed a significant association with severely impaired pulmonary function. Conclusions: The patients with PIBO had a common pattern of severe pulmonary function impairment, characterized by marked airway obstruction and pronounced increases in RV and sRaw. The combination of spirometric and plethysmographic measurements can be more useful for assessing functional damage, as well as in the follow-up of these patients, than are either of these techniques used in isolation. Known risk factors for respiratory diseases do not seem to be associated with severely impaired pulmonary function in PIBO.
Keywords: Respiratory function tests; Airway obstruction; Bronchiolitis obliterans.
Objetivo: Descrever a função pulmonar de crianças e adolescentes com bronquiolite obliterante pós-infecciosa (BOPI) e avaliar potenciais fatores de risco para pior função pulmonar. Métodos: A função pulmonar de 77 participantes, com idades de 8-18 anos, foi avaliada por meio de espirometria e pletismografia. Os seguintes parâmetros foram analisados: CVF, VEF1, FEF25-75%, VEF1/CVF, VR, CPT, VR/CPT, volume de gás intratorácico e specific airway resistance (sRaw, resistência específica das vias aéreas). Foi utilizada a regressão de Poisson para investigar os seguintes potenciais fatores de risco para pior função pulmonar: sexo, idade do primeiro sibilo, idade ao diagnóstico, história familiar de asma, exposição ao tabaco, tempo de hospitalização e tempo de ventilação mecânica. Resultados: A idade média foi de 13,5 anos. Houve uma diminuição importante de VEF1 e FEF25-75%, assim como um aumento de VR e sRaw, característicos de doença obstrutiva das vias aéreas. Os parâmetros mais afetados e as médias percentuais dos valores previstos foram VEF1 = 45,9%; FEF25-75% = 21,5%; VR = 281,1%; VR/ CPT = 236,2%; e sRaw = 665,3%. Nenhum dos potenciais fatores de risco avaliados apresentou uma associação significativa com pior função pulmonar. Conclusões: As crianças com BOPI apresentaram um padrão comum de comprometimento grave da função pulmonar, caracterizado por uma obstrução importante das vias aéreas e um expressivo aumento de VR e sRaw. A combinação de medidas espirométricas e pletismográficas pode ser mais útil na avaliação do dano funcional, assim como no acompanhamento desses pacientes. Fatores de riscos conhecidos para doenças respiratórias não parecem estar associados a pior função pulmonar em BOPI.
Descritores: Testes de função respiratória; Obstrução das vias respiratórias; Bronquiolite obliterante.
* Study carried out under the auspices of the Graduate Program in Pediatrics, Universidade Federal do Rio Grande do Sul – UFRGS,
Federal University of Rio Grande do Sul – Porto Alegre, Brazil.
Correspondence to: Rita Mattiello. Hospital da Criança Santo Antonio, Avenida Independência, 155, 5º andar, CEP 90035-074,
Porto Alegre, RS, Brasil.
Tel 55 51 3214-8646. E-mail: [email protected]
Financial support: Rita Matiello is the recipient of a grant from the Brazilian Conselho Nacional de Desenvolvimento Científico e
Tecnológico (CNPq, National Council for Scientific and Technological Development).
Submitted: 11 December 2009. Accepted, after review: 15 March 2010.
** A versão completa em português deste artigo está disponível em www.jornaldepneumologia.com.br
Original Article
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Mattiello R, Mallol J, Fischer GB, Mocelin HT, Rueda B, Sarria EE
J Bras Pneumol. 2010;36(4):453-459
Methods
This was a cross-sectional study involving
children and adolescents (8-18 years of age)
with PIBO, in Brazil and Chile. The participants
were periodically monitored at one of two
tertiary care pediatric pulmonology outpatient
clinics: that of the Hospital da Criança Santo
Antonio, located in the city of Porto Alegre,
Brazil; or that of the Centro de Referencia de
Salud del Hospital El Pino, located in the city
of Santiago, Chile. The staff at both clinics
have extensive clinical experience in diagnosing
and monitoring pediatric patients with PIBO,
having done so for more than 15 years. For the
purposes of this study, we analyzed the results of
pulmonary function tests carried out in 2007. Of
the 83 patients initially eligible for inclusion in
the study, 5 presented with pulmonary function
test results that did not meet the acceptability/
reproducibility criteria of the American Thoracic
Society/European Respiratory Society (ATS/
ERS) and another declined to participate in the
study. Those 6 patients were therefore excluded.
Consequently, the final sample consisted of
77 patients: 41 in Brazil and 36 in Chile.
The criteria for a diagnosis of PIBO were
based on previous reports(1,8,13,14) and included
all of the following:
• acute, severe bronchiolitis/viral pneumonia
during the first 3 years of life in children
who had previously been healthy
• evidence of persistent airway obstruction
after the acute event (identified either
by physical examination or by pulmonary
function testing) that was unresponsive to at
least two weeks of treatment with systemic
corticosteroids and bronchodilators
• chest X-ray findings indicative of chronic
lung disease (e.g., hyperinflation,
atelectasis, airway wall thickening, and
bronchiectasis)
• mosaic pattern and air trapping on chest CT
• exclusion of other conditions that progress
to permanent respiratory symptoms,
including chronic lung diseases such
as tuberculosis, cystic fibrosis, and
bronchopulmonary dysplasia, as well as
immunodeficiency and alpha-1-antitrypsin
deficiency
Spirometric
parameters—FVC,
FEV1,
FEF25-75%, and FEV1/FVC—and plethysmographic
parameters—intrathoracic gas volume (ITGV),
Introduction
Bronchiolitis obliterans (BO) is an uncommon
form of chronic lung disease that follows a
severe insult to the lower respiratory tract. From
the pathological perspective, it is characterized
by partial or complete luminal obstruction of
the small airways by scar tissue, secondary to
inflammation and fibrosis.(1,2)
Because organ
transplantation has improved survival in patients
with lung disease patients, the incidence of
BO as a manifestation of graft rejection has
increased.(3) In children and adolescents, however,
the most common form of BO, especially in
developing countries, is postinfectious BO
(PIBO).(4)
There have been reports of PIBO on most
continents, interesting data coming from South
American countries and corresponding to the
adenovirus epidemics that occurred during the
1990s.(4-6) In PIBO, as in other chronic lung
diseases, determining pulmonary function is
crucial for the diagnosis, as well as for classifying
the severity of the condition and monitoring
its progression. Unfortunately, there is only
sparse information in the literature regarding
the pulmonary function of patients with PIBO.
Two studies (both conducted by the same
research group) evaluated pulmonary function
in infants with PIBO.(5,7)
Those two studies
produced consistent results, since both included
a representative number of patients. That is
not the case for studies involving children and
adolescents with PIBO; the few articles providing
lung function data usually have small sample
sizes and different methodology or focus, which
precludes an appropriate characterization of
LF.(8-11) This effectively prevents us from drawing
reliable conclusions regarding the characteristics
of pulmonary function in this age bracket.
Profiling the pulmonary function of children
and adolescents with PIBO could give us a better
insight of the long-term respiratory effects of
the disease. This could be of interest not only
to those studying and treating patients with
PIBO, but also to those in the field of lung
transplantation, since the histopathological
similarities between transplant and PIBO(12) could
translate to similarities in pulmonary function.
The objective of this study was to describe the
pulmonary function of children and adolescents
with PIBO and to evaluate the potential risk
factors for severe impairment of pulmonary
function.
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Pulmonary function in children and adolescents with postinfectious bronchiolitis obliterans
J Bras Pneumol. 2010;36(4):453-459
455
by a forced expiratory maneuver in which the
patient exhaled down to RV. The effort with
the greatest VC and the best shutter maneuver,
which included the loop closest to the pressure-
volume axis, was considered the best effort.
Spirometric measurements were taken after the
patient had rested for 5 min. Appropriate values
were selected from the best three acceptable and
reproducible FVC maneuvers, and the selected
maneuver was the one with the greatest sum of
FVC and FEV1.
We employed the reference values and
equations devised by Perez-Padilla et al. and
Zapletal et al. for spirometry and plethysmography,
respectively.(18,19) All pulmonary function data
are expressed as a percentage of the predicted
reference value. The severity of impairment
for spirometric parameters was based on FEV1
according to the ATS/ERS recommendations,(20)
and the normality ranges accepted for volumes
were those recommended by the Sociedad
Española de Neumología y Cirugía Torácica
(Spanish Society of Pulmonology and Thoracic
Surgery).(21)
We defined severely impaired
pulmonary function as that classified as severe
or very severe impairment, according to the ATS
criteria.(20)
Continuous variables are expressed as mean
and 95% CI, whereas categorical variables are
expressed as absolute and relative frequency.
The adjusted prevalence ratios of potential risk
factors for severe impairment of pulmonary
function were calculated by Poisson regression
with robust error variance in bivariate and
multivariate analyses. This was followed by an
interactive procedure, initially considering all
covariates with a p value < 0.10 in a multiple
regression model. The covariates with the
RV, TLC, RV/TLC, and specific airway resistance
(sRaw)—were measured in accordance with
international recommendations for acceptability
and reproducibility.(15,16) The pulmonary function
parameters were measured only if patients
had been free of respiratory exacerbations
and clinically stable for at least two weeks.
Short-acting and long-acting β2 agonists were
withheld for, respectively, 12 h and 48 h prior
to the tests, although inhaled corticosteroids
were maintained as prescribed. Before any tests
were conducted, the patients were familiarized
with the basic maneuvers for spirometric and
plethysmographic measurements.
At each facility, the measurements were
conducted by an accredited laboratory technician.
All measurements were taken in the morning
(plethysmography followed by spirometry).
Both centers used the same type of spirometer
(MasterScreen Body, with software, v4.3; Jaeger,
Würtzburg, Germany), which was calibrated daily
using a 3-L syringe, and measurements were
electronically corrected to body temperature and
pressure, saturated conditions.(15-17)
During the plethysmography, the patients
were instructed to breathe calmly through a
mouthpiece until reaching a stable end-expiratory
level. The shutter then closed automatically for
2-3 s while the patients performed a series of
shallow panting maneuvers (against 0.5-1.0 Hz
of resistance), with both hands supporting their
cheeks. The results of three to five technically
satisfactory maneuvers were registered for
subsequent analysis. The shutter was opened,
and the patients slowly exhaled as completely as
possible (to allow the expiratory reserve volume
to be determined). Subsequently, the patients
slowly inhaled up to TLC, and this was followed
Table 1 – Demographic data of the participants, by country.
Variable
Brazil
Chile
Both countries
(n = 41)
(n = 36)
(n = 77)
Age,a years
11.5 (10.7-12.3)
15.1 (14.0-16.3)
13.3 (12.4-14.0)
Height,a cm
144.6 (139.7-149.5)
157.3 (152.6-162.0)
150.5 (146.9-154.1)
BMI,a kg/m2
17.9 (16.9-18.9)
21.4 (20.0-22.9)
19.5 (18.6-20.5)
Age at diagnosis,a months
12.2 (9.6-14.6)
10.78 (8.2-13.3)
11.4 (9.7-13.2)
0-6b
7 (17.1)
9 (25.0)
16 (20.8)
7-12b
22 (53.6)
17 (47.2)
39 (50.6)
13-24b
10 (24.4)
9 (25.0)
19 (24.7)
>24b
2 (4.9)
1 (2.8)
3 (3.9)
Male genderb
31 (75.6)
19 (52.8)
50 (64.9)
aValues expressed as mean (95% CI). bValues expressed as n (%).
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Mattiello R, Mallol J, Fischer GB, Mocelin HT, Rueda B, Sarria EE
J Bras Pneumol. 2010;36(4):453-459
RV, RV/TLC, and sRaw) were markedly high, with
the exception of TLC, which was within normal
limits.
In the regression model, none of the potential
risk factors demonstrated a significant association
with severely impaired pulmonary function. There
was a moderate correlation between RV/TLC and
FEV1 (r = −0.657, p < 0.001) and between RV/
TLC and FEF25-75% (r = −0.669, p < 0.001).
Discussion
The present study describes pulmonary
function in one of the largest samples of
pediatric patients with PIBO evaluated to date.
Our results show that, at both of the facilities
involved, the children and adolescents with PIBO
presented with moderate to very severe airway
obstruction.(20) This impairment, which probably
reflects major chronic damage of the medium
and small airways, is characterized by decreased
expiratory airflow, together with increased RV
and sRaw.
In order to elucidate the great impact that
PIBO has on the major morphological and
functional components of the respiratory system,
a combination of methods must be employed.
One such method is pulmonary function testing,
which allows us to assess, in a relatively practical
and noninvasive manner that is most suitable
for diagnostic and follow-up routines, how the
viscoelastic and flow-resistive properties of the
system are impaired.(22)
Because PIBO is a rare disease with a relatively
small number of patients in any given country,
the use and results of pulmonary function testing
highest p values were removed from the model,
which was then recalculated. The final model
comprised only covariates with a p value < 0.10.
We included the following variables as potential
risk factors: ggender; age at first wheeze;
age at diagnosis; family history of asthma;
tobacco smoke exposure; length of hospital
stay; and duration of mechanical ventilation.
The correlation between RV/TLC and FEV1, as
well as that between RV/TLC and FEF25-75%, was
assessed using Pearson’s correlation coefficient
(r). The level of statistical significance was set
at p < 0.005.
The study was approved by both local
research ethics committees. The parents or
legal guardians of the participants gave written
informed consent, and the participating patients
verbally agreed to be included in the study.
Results
The demographic data are shown in Table 1.
In both groups, there was a predominance of
males (Brazil: 75.6%; Chile: 52.8%). The overall
means (and the group means for Brazil and Chile,
respectively) were as follows: age, 13.3 years
(11.5 and 15.1 years); height, 150.5 cm (144.6
and 157.3 cm); and BMI, 19.5 kg/m2 (17.9 and
21.4 kg/m2). The onset of the disease occurred
between 1 and 24 months of age in most of the
patients (97% of the group in Brazil and 97% of
the group in Chile).
Table 2 shows the pulmonary function
parameters. In both groups, the mean values
of all spirometric variables, especially FEV1 and
FEF25-75%, were low. Correspondingly, the mean
values of most plethysmographic variables (ITGV,
Table 2 – Pulmonary function parameters of the participants, by country.
Parametera
Brazilb
Chileb
Both countriesb
(n = 41)
(n = 36)
(n = 77)
FVC
61.7 (56.9-66.4)
72.5 (68.2-76.8)
66.8 (63.4-70.2)
FEV1
42.5 (37.6-47.0)
49.7 (44.7-54.8)
45.9 (42.4-49.4)
FEF25-75%
19.9 (16.0-23.8)
23.4 (19.1-27.7)
21.5 (18.6-24.4)
FEV1/FVC
67.6 (63.1-72.1)
66.8 (62.5-71.1)
67.2 (64.1-70.3)
TLC
116.8 (113.1-120.5)
112.5 (10.8-117.1)
116.8 (113.2-120.5)
ITGV
162.7 (154.0-171.4)
144.5 (134.6-154.3)
162.7 (154.0-171.4)
RV
281.1 (258.6-303.7)
231.0 (203.2-258.7)
281.1 (258.6-303.7)
RV/TLC
236.2 (222.5-250.40)
200.9 (184.7-217.1)
236.2 (222.5-250.0)
sRaw
746.6 (597.5-895.7)
572.8 (431.9-713.6)
665.3 (562.5-768.2)
ITGV: intrathoracic gas volume; and sRaw: specific airway resistance. aValues expressed as percentage of the predicted
value. bValues expressed as mean (95% CI).
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when airflow obstruction becomes more severe
as a result of decreased lung elastic recoil or
changes in dynamic mechanisms, ITGV, RV, TLC,
and RV/TLC tend to increase.
We found only two studies evaluating lung
volumes in pediatric patients with PIBO.(9,10)
We pooled the data of their collective sample
(n = 25) and, disregarding any methodological
differences, found that all of the patients
showed a marked increase in RV. In our study
sample (n = 77), we also identified patients
with reduced FVC. However, in those patients,
the TLC was also considerably above 80% of
the predicted value, with a noticeable increase
in RV and RV/TLC. These lung volume data,
obtained by plethysmography, leave no doubt as
to the obstructive nature of PIBO. In addition,
we found that, overall, RV/TLC presented
good correlations with two of the spirometric
parameters, FEV1 and FEF25-75%, indicating that
the degree of hyperinflation paralleled the
severity of airway obstruction. This situation
can lead to progressive clinical consequences,
such as a permanent need for oxygen therapy or
impaired quality of life.
Although FEV1/FVC and FEV1
are the
spirometric parameters most often employed
in order to determine airway obstruction,
FEF25-75% has also been considered a relevant early
indicator of this abnormality, since it appears to
show a proportionately greater reduction than
does FEV1 or FEV1/FVC.(9,10,20) Our results show
that all of the patients had abnormal values
for FEF25-75%
and FEV1, the FEF25-75%
value
being half of that obtained for FEV1. This is in
agreement with the current recommendations
for diagnosing bronchiolitis obliterans syndrome
(BOS) in transplant patients. Since FEF25-75% has
been found to deteriorate sooner after BOS onset
than does FEV1,(3) the criteria for early detection
of BOS now include a decline in FEF25-75%, as
well as a decrease in FEV1.(26) Because FEF25-75%
presents considerable variability, as evidenced
in a recent study,(27) its routine use in clinical
practice has been controversial. However, its
considerable and consistent reduction in our
patients with PIBO suggests that FEF25-75% should
be considered together with the established duo
of FEV1 and FEV1/FVC to define the extent of
functional damage, as well as in the routine
follow-up of such patients. The fact that it is
obtained simultaneously with other spirometric
in PIBO patients have been addressed in only a
few studies, six of which have been notable:
• Studying a sample of 13 infants in
Argentina, Teper et al. suggested that the
functional impairment caused by PIBO is
established at its early stages.(7)
• Kim et al. described the pulmonary
function of 14 children within a study
group of 31 children with PIBO in the USA
and South Korea. The authors found that
all 14 presented with severe, fixed airway
obstruction.(9)
• Castro-Rodriguez et al., using the impulse
oscillometry technique, found evidence
of peripheral airway dysfunction in 18
preschool children in Chile.(23)
• Cazzato et al. conducted a longitudinal
study of the pulmonary function of 14
children in Italy and found an annual
decline of 1% in the predicted values of
FEV1, FEV1/FVC and FEF25-75%.(10)
• In Brazil, Mattiello et al. assessed the
functional capacity of 20 children during
cardiopulmonary exercise testing and
compared the results with those of
conventional pulmonary function testing.
The children presented with reduced
oxygen consumption, which correlated
positively with FVC, FEV1, and RV/TLC.(11)
• Mattiello et al. also studied a group of
21 children in Brazil and showed that the
CT findings in early life seem to predict
severely impaired pulmonary function a
decade later.(24)
Our results corroborate and expand upon a
conclusion drawn on the basis of those studies:
the functional hallmark of the disease is marked
airway obstruction with air trapping. Another
group of authors described PIBO patients
with a restrictive or mixed pattern of obstruction.
(25) However, those authors based their analysis
solely on a reduced FVC that was associated with
a normal or low FEV1/FVC ratio.(25) Therefore,
their finding can be explained in the context of
a considerable airway obstruction that leads to
pronounced air trapping, the degree of which is
best determined through the assessment of lung
volumes.(20) The ATS and ERS both recommend
the determination of lung volumes in patients
with obstructive lung diseases, such as PIBO,
because it allows a better understanding of the
underlying respiratory impairment.(16,20) In fact,
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Mattiello R, Mallol J, Fischer GB, Mocelin HT, Rueda B, Sarria EE
J Bras Pneumol. 2010;36(4):453-459
www.thoracic.org/global-health/mecor-
courses/mecor-program-description.pdf), for
their support and suggestions regarding this
manuscript.
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15. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi
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parameters and through the same technique
strengthens its feasibility.
One limitation of our study is that our two
groups of patients with PIBO were each from a
different country. However, since both of those
countries are in the southern portion of South
America, there are geographic, ethnic, and
nutritional similarities between the two groups. In
addition, they all developed the disease at similar
(young) ages, corresponding to simultaneous
regional bursts of severe adenovirus respiratory
infections during the early and mid 1990s.(28)
Furthermore, the measurements corresponded
to pulmonary function testing obtained during
the same year, both pulmonary function testing
laboratories are board certified, both follow the
ATS/ERS recommendations, and both used the
same apparatus and software. The group results
are presented together with those of the sample
as a whole, and it is clear that the two patient
groups were similar in terms of pulmonary
function.
Our sample size was adequate to run the
statistical model used, and our analyses revealed
that none of the factors studied constituted a risk
for severe impairment of pulmonary function.
We believe that the value of our study lies
in the large number of participants and the
broad age range of the sample, as well as in
the use and analysis of an extensive number
of pulmonary function variables. These aspects
allowed us to obtain data that are consistent and
reliable. Our data can inform decisions regarding
the evaluation and treatment of patients with
PIBO, as well as those regarding future studies in
children or adolescents with post-transplant BO.
In conclusion, pediatric patients with PIBO
have a common pattern of severe pulmonary
function impairment, characterized by
marked airway obstruction and a pronounced
increase in RV and sRaw. Our results suggest
that the combined use of spirometric and
plethysmographic measurements is more useful
than is that of each method alone in assessing
functional damage at a given time and in the
follow-up of children or adolescents suffering
from this rare disease.
Acknowledgments
The authors wish to thank Dr. Sonia Buist
and Dr. Gordon Rubenfeld, both of whom are
professors for the ATS-MECOR Course (http://
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Sobre os autores
Rita Mattiello
Doctoral Fellow in Pediatrics. Universidade Federal do Rio Grande do Sul – UFRGS, Federal University of Rio Grande do Sul – School
of Medicine, Porto Alegre, Brazil.
Javier Mallol
Physician. Department of Pediatric Respiratory Medicine, Centro de Referencia de Salud del Hospital El Pino – Hospital-CRS El Pino,
El Pino Referral Hospital – University of Santiago, Santiago, Chile.
Gilberto Bueno Fischer
Professor of Pediatrics. Universidade Federal de Ciências da Saúde de Porto Alegre – UFCSPA, Federal University of Health Sciences
of Porto Alegre, Porto Alegre, Brazil.
Helena Teresinha Mocelin
Physician. Pediatric Pulmonology Sector, Hospital da Criança Santo Antônio, Porto Alegre, Brazil.
Belkys Rueda
Physician. Department of Pediatric Respiratory Medicine, Centro de Referencia de Salud del Hospital El Pino – Hospital-CRS El Pino,
El Pino Referral Hospital – University of Santiago, Santiago, Chile.
Edgar Enrique Sarria
Research Fellow in Pediatric Pulmonology. Indiana University, Indianapolis (IN) USA.
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