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INTERNATIONAL JOURNAL OF THORAX
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Research
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Impact Of Bronchiectasis On COPD Exacerbations
Antonio Molino1,*, Carolina Vitale2, Tullio Valente3, Maria D’Amato1, Mauro Mormile1, Pasquale Imitazione1,
Angelantonio Maglio2, Alessandro Vatrella2
1
Respiratory Department Federico II University- A.O. "Dei Colli",Naples, Italy
2
Department of Medicine, Surgery and Dentistry, Section of Respiratory Diseases, University of Salerno, Salerno,
Italy
3
Division of Radiology, Department of Diagnostic Imaging, Monaldi Hospital
Abstract
The presence of bronchiectasis is considered an aggravating factor in COPD patients. In particular, the
coexistence of bronchiectasis and COPD was associated with greater frequency and severity of exacerbations.
The aim of this study is to investigate the impact of bronchiectasis in patients with COPD exacerbation.
We retrospectively collected data from 212 patients admitted to the hospital with diagnosis of COPD
exacerbation. In order to detect the presence of bronchiectasis, only patients that had received a chest HRCT
scan examination were included in the study. We compared clinical and functional
data between COPD
patients with bronchiectasis and those without bronchiectasis.
The prevalence of bronchiectasis was 31,6% in this study. The presence of bronchiectasis in COPD
patients was associated with increased risk for isolation of PPMs in the airway (56,1% vs 28,3%, p 0,02), and
in particular of Pseudomonas Aeruginosa (17,5% vs 5,6% p 0,02), and with a longer duration
of
hospitalization (8,22 ±3,67 vs 6,88 ± 3,43 days, p=0.004).
These results could encourage efforts to optimize medical care for patients with COPD and
bronchiectasis. Clinical trials with treatments for infective component are needed to investigate their impact on
the reductions of exacerbations and improvements in the disease course.
Corresponding Author: Antonio Molino, Respiratory Department Federico II University- A.O. "Dei Colli" Via
Leonardo Bianchi 1, 80131-Naples, Italy. Email: molinotonio@libero.it
Keywords: COPD, Bronchiectasis, exacerbations
Received: Jan 27, 2018
Accepted: Apr 04, 2018
Published: Apr 07, 2018
Editor: Mohamed Shahat Badawy Ahmed, Assistant Professor of Chest Diseases Head of Chest Department,
Qena Faculty of Medicine, South Valley University, Egypt.
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In this study we aim to analyze the impact of
Introduction
Chronic obstructive pulmonary disease (COPD)
is one of the leading causes of morbidity and mortality
bronchiectasis on patients with COPD exacerbation.
Methods
In this retrospective study we collected data
worldwide with a substantial social and economic
burden [1]. It’s a complex disease with different clinical
from
212
features and treatment responses [2-6]. In recent years,
Pneumology Unit of Monaldi Hospital in Naples between
there has been a growing interest in identifying COPD
2010 and 2014, with diagnosis of exacerbation of COPD.
phenotypes, in order to provide more individualized
In order to detect the presence of bronchiectasis, only
treatment strategies [2-6]. High-resolution computed
patients
tomography (HRCT) of the lungs may provide a way to
examination were included in the study. Written
define a distinct COPD phenotype by investigating the
informed consent was obtained from all of the patients.
main relevant morphological findings such as the
The study was approved by hospital Ethic Committee.
presence of emphysema, bronchial wall thickening, and
bronchiectasis [9-12].
Bronchiectasis is defined as irreversible and
that
had
patients
received
a
admitted
chest
to
HRCT
the
scan
Clinical characteristics were recorded for each
patient,
generally progressive dilation of the airways, usually as
consecutive
including
lung
function,
smoking
history,
comorbidities and number of COPD exacerbations in the
previous year.
a result of chronic airway inflammation and/or infection.
COPD was confirmed by the presence of a
The impact of bronchiectasis on COPD was
post-bronchodilator forced expiratory volume in 1
assessed in several studies [13-16]. Determining the
second/forced
precise prevalence of bronchiectasis in COPD is difficult;
according to the criteria published by the GOLD
existing data indicate a huge variability in bronchiectasis
document [1].
prevalence, ranging from 4 to 72%. However, there is
agree to consider bronchiectasis an aggravating factor
in COPD patients [11-16].
properly suggest a different clinical COPD phenotype
[1,15,21]. In particular, the presence of bronchiectasis
in COPD has been associated with greater frequency
and severity of exacerbations [22-24].
An
exacerbation
of
COPD
or
increased
defined
sputum
volume
or
treatment with oral corticosteroids or antibiotics [1,25].
Patients with mild or moderate COPD exacerbation can
be managed at home, while patients with severe
may
need
hospitalization
[1,25].
Hospitalizations for COPD exacerbation are associated
with increased mortality and impaired health-related
quality of life. Furthermore hospitalizations for COPD
exacerbation
account for more than 70% of all
COPD-related health care costs [1,25].
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70%
symptoms
that
results
in
additional
therapy [1].
The diagnosis of bronchiectasis was confirmed
by a chest HRCT scan. High-resolution images were
obtained in full inspiration at 1-mm collimation and
10-mm intervals from the apex to the base of the lungs.
Based on the morphology, bronchiectasis was defined as
as
purulence beyond the basal variability and that required
symptoms
<
cylindrical, cystic and mixed.
is
sustained worsening of respiratory symptoms, such as
breathlessness
(FEV1/FVC)
event characterized by a worsening of the patient’s
COPD [1], nevertheless this definition may be reductive.
In fact, the coexistence of bronchiectasis and COPD may
capacity
COPD exacerbation was defined as an acute
respiratory
Bronchiectasis was defined as a comorbidity of
vital
CC-license
α1-antitrypsin deficiency, serum immunoglobulin
deficiencies, IgE and IgG to Aspergillus fumigatus and
cystic fibrosis were excluded in all patients with
bronchiectasis.
During
hospitalization
each
patient
was
requested to collect samples of spontaneous mornig
sputum for the microbiologic analysis. Samples were
processed
by
the
reference
clinical
microbiology
laboratory using standard procedure [26-29]. The
suitability of the sputum sample for the culture was
assessed with Q score, examining leukocytes and
epithelia cells by gram stain (Q1: 0 epithelial cells and
1-9 leukocytes per field or < 10 epithelial cells and
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10-24 leukocytes per field or < 25 epithelial cells and
Clinical and functional data were compared between the
>25 leukocytes. Q2: 0 epithelial cells and 10-24
two groups.
leukocytes per field or 1-9 epithelial cells and > 25
leukocytes per field. Q3: 0 epithelial cells and > 25
leukocytes per field) [26,27].
Samples with a Q score ≥ 1 were considered
representative
of distal
airways and
subsequently
processed for culture. Bacterial growth was assessed at
48 hours and fungal growth at 72 hours. The airway
bacteria
cultured
were
classified
into
potential
pathogenic microorganisms (PPMs) and non-PPMs, as
previously described [28].
Based on previously published methods, sputum
cultures were expressed as colony-forming units (CFUs)
per mL and a cutoff point of 103 CFUs/mL or more was
defined as significant for the identification of abnormal
positive culture results for PPM [29]. Isolated bacterial
agents were classified into PPMs strains, including
Pseudomonas Aeruginosa, Streptoccocus Pneumoniae,
Moraxella
Catarralis,
Staphiloccocus
Aureus,
Haemophilus
Klebsiella
Influenzae,
pneumonia,
Escherichia coli, Mycobacterium tubercolosis, Candida
albicans and other pathogenic microorganisms.
The entire patient population had moderate to
severe COPD.
The presence of bronchiectasis was associated
with a higher number of exacerbations in the previous
year (p 0,00001).
The smoking history, expressed as pack/years,
was
significant
in
COPD
patients
without
bronchiectasis (p 0,0001).
FEV1, FVC, PaO2, PaCO2 of patients, as well as
the Charlson Index score, didn’t significantly vary
between the two groups. An average of 3 valid sputum
samples was collected from patients who had daily
sputum production during the hospitalization. COPD
patients with bronchiectasis had a higher prevalence of
PPMs colonization (p=0,02). Candida Albicans was the
most frequently isolated
PPM in the entire patient
population (62 patients). The isolation of Pseudomonas
Aeruginosa was significantly most frequent in COPD
patients with bronchiectasis than in those without
bronchiectasis (p=0,02), while the isolation of other
PPMs was not significant different between the two
Statistics
groups. Mycobacterium tuberculosis and nontuberculosis
The statistical software SPSS, version 20, was
mycobacteria weren’t detected in any samples.
used for the statistical analysis. The Student T test for
indipendent variables was used to analyze variables that
were normally distributed and the Mann-Whitney U test
was used to analyze variables that were non-normally
distributed. The chi-square test was used to compare
qualitative variables. A p-value less than 0.05 was
considered to be statistically significant.
Overall, data from 212 patients with COPD
exacerbation were retrospectively analyzed (mean age ±
SD 71,3 ± 8,5; 79,2% men). Based on HRCT evidence
of bronchiectasis, the patients were divided
into two
groups: patients with bronchiectasis (n=67, 31,6%) and
patients without bronchiectasis (n=145, 69,4%). Other
conditions that can trigger bronchiectasis were excluded
deficiency,
serum
No
samples
or
unqualified
samples
were
collected from 49 patients (23,1%).
The presence of bronchiectasis in patients with
COPD was associated with a longer duration of
hospitalization (8,22 ±3,67 vs 6,88 ± 3,43 days,
p=0.004)
The differential characteristics of the two groups
Results
(α1-antitrypsin
more
immunoglobulin
deficiencies, IgE and IgG to Aspergillus fumigatus, cystic
fibrosis). Bronchiectasis was cylindrical in 85% of cases.
are reported in tables 1 and 2.
Discussion
In this small study, we evaluated the impact of
bronchiectasis on patients with COPD exacerbation.
The prevalence of bronchiectasis in COPD patients was
31,6%. This finding is similar to the percentage reported
in previous studies [6-11]. 85% of patients had
cylindrical bronchiectasis. Although there is still much to
understand about the interaction between COPD and
bronchiectasis,
the
high
rate
of
coexistence
of
bronchiectasis and COPD could be explained by shared
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Table 1. Baseline and clinical characteristics of subjects with COPD, with and without bronchiectasis. Data
are presented as n (%) or mean ± SD.(Statistical tests: T-student test, Mann-Whytney Test)
Whole Group
COPD with
COPD without
Bronchiectasis
Bronchiectasis
p
Subjects
212
67 (31,6%)
145 (68,39%)
Sex, M/F
168/44
119/26
49/18
Age,Y
71,33 ± 8,48
69,97 ± 9,8
71,48 ± 9,61
0,11
Smoking History-pack/years
24,95± 10,78
20,3 ± 10,19
27,18 ± 10,28
0,0001
1,14 ±0,8
1,57±0,74
0,94±0,75
0,00001
FVC
63,33 ± 14,66
60,94 ± 12
64,44 ± 15,66
0,1
FEV1
46,84 ± 13,55
46,59 ± 10,53
46,96 ± 14,75
0,85
pO2 mmHg
62,97 ± 11,4
62,08 ± 10,38
63,39 ± 11,34
0,42
pCO2 mmHg
57,04 ± 13,91
43,30 ± 7,58
44,32 ± 7,15
0,34
Charlson Index
2,16 ± 0,68
2,06 ± 0,69
2,21 ± 0,66
0,15
Length of hospitalization
7,30 ± 3,55
8,22 ± 3,67
6,88 ± 3,43
0,004
Number of Exacerbations in
the previous year
Table 2. Microbiological characteristics of subjects with COPD, with and without bronchiectasis. Data are
presented as n (%) or mean ± SD. (Statistical test : Chi-Square)
Whole Group 163
COPD with
COPD without
Bronchiectasis 57
Bronchiectasis 106
p
Haemophilus Influenzae
26 (15,9%)
8(14%)
18 (16,9%)
0,6
Streptococcus Pneumoniae
17 (10,4%)
5 (8,7%)
12 (11,3%)
0,6
Moraxella Catarrhalis
16 (9,8%)
5(8,7%)
11(10,3%)
0,7
Pseudomonas Aeruginosa
16 (9,8%)
10 (17,5%)
6 (5,6%)
0,02
Staphiloccocus Aureus
7 (4,2%)
4(7%)
3 (2,8%)
0,2
Escherichia Coli
6 (3,6%)
3 (5,2%)
3 (2,8%)
0,4
Klebsiella Pneumoniae
4 (2,4%)
2 (3,5%)
2 (1,8%)
0,5
Candida Abicans
62 (38%)
18 (31,5,8%)
44(41,5%)
0,3
62 (38%)
32 (56,1%)
30 (28,3%)
0,02
Patients with at least one
PPM isolate
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pathological mechanisms. In fact, chronic inflammation
frequency of exacerbations, it’s clear that the detection
of airway has a key role in the pathogenesis of both
of bronchiectasis in COPD by performing an HRCT scan
conditions and tobacco exposure is considered a causal
should be encouraged in order to identify these patients
factor in both diseases[30-33].
and
The presence
of
provide
the
most
effective
treatment.
The
bronchiectasis in COPD patients was associated with a
coexistence of bronchiectasis and COPD should expect
greater number of exacerbations in the previous year.
more appropriate treatment for the infective component
The association between bronchiectasis and a greater
of the disease. Unfortunately, data about therapies for
frequency of exacerbations is widely recognized [22-24].
COPD complicated by bronchiectasis are not available,
This is probably due to permanent dilatation of the
due to the lack of clinical trials in this population. Based
airways and impairment of mucociliary clearance that
on trials on bronchiectasis, including smokers with
can lead to bacterial colonization. Bacterial colonization
airflow obstruction which is not fully reversible and
can trigger an intense inflammatory response which
similar to COPD, some Authors have suggested that the
damages local defense mechanism. This interaction
use of long-term macrolides or inhaled antibiotics could
between
systemic
be beneficial in reducing exacerbations in COPD patients
inflammation may lead to frequent exacerbations, as
with bronchiectasis. Physiotherapy should also be
well as other distinctive clinical features as more sputum
considered
production [24].
patients [15,36,37].
chronic
PPM
colonization
and
About pulmonary function data, the entire
patient population had moderate to severe COPD.
as
an
useful
groups. This result is opposite to the findings of
previous studies in which bronchiectasis was associated
with more severe bronchial obstruction[18-20]. This
discrepancy may be explained by several reasons.
Firstly, the small sample size in the present study
economic burden on the healthcare system.
related
to
exacerbations,
hospitalization[1,39].
Based
health
care
costs
(longer
Conclusion
presence
of
bronchiectasis was associated with increased prevalence
of PPMs colonization and in particular of Pseudomonas
Aeruginosa.
The
association
of
chronic
PPMs
colonization, as well as P. Aeruginosa isolation, with
bronchiectasis
was
confirmed
by
several
studies [22-24,34]. The presence of PPMs and the
consequent chronic inflammation result in remodeling of
the airways and facilitate the persistence of PPMs in the
bronchial
mechanism
tree.
that
These
factors
generates
may
trigger
bronchiectasis
the
[15,35].
Furthermore, Pseudomonas Aeruginosa was isolated
from 3% to 20% of patients with COPD and, more
frequently, from patients with severe disease and during
exacerbations [37]. COPD patients with bronchiectasis
had a longer length of hospitalization. This is may be
justified by the need of more prolonged antibiotic
therapies. Considering these data and the higher
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in
on
particular
to
results,
the
our
coexistence of bronchiectasis and COPD leads to higher
study, COPD patients with bronchiectasis had a less
The
A
substantial portion of the total burden of COPD is
provides insufficient statistical power. Secondly, in this
history.
these
The presence of bronchiectasis in COPD patients
prolonged antibiotic therapies].
smoking
in
has a significant impact on disease course as well as on
FEV1 didn’t significantly vary between the two
significant
strategy
hospitalizations,
more
In conclusion, data obtained from the present
study indicate that the presence of bronchiectasis in
patients with COPD exacerbation was associated with an
increased risk of isolation of PPMs, in particular of
Pseudomonas Aeruginosa, and with a longer duration of
hospital stay. These results could encourage efforts to
optimize medical care for patients with COPD and
bronchiectasis.
Clinical
trials
with
treatments
for
infective component are needed to investigate their
impact
on
the
reductions
of
exacerbations
and
improvements in the disease course.
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