Background: Asthma and bronchiectasis are 2 heterogeneous diseases that frequently coexist, particularly in severe asthma. Recognition of this co-diagnosis may importantly affect treatment decisions and outcome. Previous studies in asthma with bronchiectasis show inconsistent outcomes, probably due to the heterogeneity of the included asthma cohorts. Objectives: We hypothesized that bronchiectasis contributes to asthma severity and that patients with severe asthma and bronchiectasis present with distinct characteristics resulting in different treatable traits. In addition, we explored whether bronchiectasis in severe asthma is more common in a specific phenotype. Methods: This is a single-center study consecutively including patients with severe asthma from a tertiary referral center. Severe asthma was diagnosed according to the ATS/ERS guidelines. Asthma and infectious exacerbations were defined by the attending specialist as respiratory symptoms requiring treatment with systemic steroids or antibiotics, respectively. Two independent blinded radiologists evaluated each CT. Results: 19% of patients with severe asthma showed bronchiectasis on CT. Patients with bronchiectasis had a lower FEV1% predicted (p = 0.02) and FEV1/FVC (p = 0.004) and more infectious exacerbations (p = 0.003) compared to patients without bronchiectasis. Bronchiectasis is more common in patients with a longer duration of asthma, sensitization to A. fumigatus or a positive sputum culture. Sputum cultures of patients with severe asthma and bronchiectasis revealed more P. aeruginosa, S. maltophilia, H. parainfluenzae, and A. fumigates compared to the non-bronchiectasis group. The adult-onset, eosinophilic asthma phenotype showed the highest prevalence of bronchiectasis (29.4%). Conclusions: Patients with severe asthma and coexisting bronchiectasis were found to represent a distinct group, in terms of disease severity, microbiology, and asthma phenotype. Performing (HR)CT and sputum cultures can help to identify these patients. These results can possibly contribute to early recognition and targeted treatment of this patient group.

1.
Hekking
PP
,
Wener
RR
,
Amelink
M
,
Zwinderman
AH
,
Bouvy
ML
,
Bel
EH
.
The prevalence of severe refractory asthma
.
J Allergy Clin Immunol
.
2015
;
135
(
4
):
896
902
. .
2.
Chung
KF
,
Wenzel
SE
,
Brozek
JL
,
Bush
A
,
Castro
M
,
Sterk
PJ
, et al
International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma
.
Eur Respir J
.
2014
;
43
(
2
):
343
73
. .
3.
Porsbjerg
C
,
Menzies-Gow
A
.
Co-morbidities in severe asthma: clinical impact and management
.
Respirology
.
2017
;
22
(
4
):
651
61
. .
4.
Andrejak
C
,
Nielsen
R
,
Thomsen
VO
,
Duhaut
P
,
Sorensen
HT
,
Thomsen
RW
.
Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis
.
Thorax
.
2013
;
68
(
3
):
256
62
.
5.
Carpagnano
GE
,
Scioscia
G
,
Lacedonia
D
,
Curradi
G
,
Foschino Barbaro
MP
.
Severe uncontrolled asthma with bronchiectasis: a pilot study of an emerging phenotype that responds to mepolizumab
.
J Asthma Allergy
.
2019
;
12
:
83
90
. .
6.
Henkle
E
,
Aksamit
TR
,
Barker
AF
,
Curtis
JR
,
Daley
CL
,
Anne Daniels
ML
, et al
Pharmacotherapy for non-cystic fibrosis bronchiectasis: results from an NTM info & research patient survey and the bronchiectasis and NTM research registry
.
Chest
.
2017
;
152
(
6
):
1120
7
.
7.
Stefan
MS
,
Shieh
MS
,
Spitzer
KA
,
Pekow
PS
,
Krishnan
JA
,
Au
DH
, et al
Association of antibiotic treatment with outcomes in patients hospitalized for an asthma exacerbation treated with systemic corticosteroids
.
JAMA Intern Med
.
2019
;
179
(
3
):
333
9
.
8.
Wang
D
,
Luo
J
,
Du
W
,
Zhang
LL
,
He
LX
,
Liu
CT
.
A morphologic study of the airway structure abnormalities in patients with asthma by high-resolution computed tomography
.
J Thorac Dis
.
2016
;
8
(
10
):
2697
708
. .
9.
Hansell
DM
,
Bankier
AA
,
MacMahon
H
,
McLoud
TC
,
Müller
NL
,
Remy
J
.
Fleischner society: glossary of terms for thoracic imaging
.
Radiology
.
2008
;
246
(
3
):
697
722
. .
10.
McDonald
VM
,
Hiles
SA
,
Godbout
K
,
Harvey
ES
,
Marks
GB
,
Hew
M
, et al
Treatable traits can be identified in a severe asthma registry and predict future exacerbations
.
Respirology
.
2019
;
24
(
1
):
37
47
. .
11.
de Groot
JC
,
Storm
H
,
Amelink
M
,
de Nijs
SB
,
Eichhorn
E
,
Reitsma
BH
, et al
Clinical profile of patients with adult-onset eosinophilic asthma
.
ERJ Open Res
.
2016
;
2
(
2
). .
12.
Charlson
ME
,
Pompei
P
,
Ales
KL
,
MacKenzie
CR
.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
.
J Chronic Dis
.
1987
;
40
(
5
):
373
83
. .
13.
Reddel
HK
,
Taylor
DR
,
Bateman
ED
,
Boulet
LP
,
Boushey
HA
,
Busse
WW
, et al
An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice
.
Am J Respir Crit Care Med
.
2009
;
180
(
1
):
59
99
. .
14.
Quanjer
PH
,
Tammeling
GJ
,
Cotes
JE
,
Pedersen
OF
,
Peslin
R
,
Yernault
JC
.
[Lung volumes and forced ventilatory flows. Work group on standardization of respiratory function tests. European community for coal and steel. Official position of the European Respiratory Society]
.
Rev Mal Respir
.
1994
;
11
(
Suppl 3
):
5
40
.
15.
American Thoracic S, European Respiratory S
.
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
(
8
):
912
30
. .
16.
Agarwal
R
,
Chakrabarti
A
,
Shah
A
,
Gupta
D
,
Meis
JF
,
Guleria
R
, et al
Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria
.
Clin Exp Allergy
.
2013
;
43
(
8
):
850
73
. .
17.
Reiff
DB
,
Wells
AU
,
Carr
DH
,
Cole
PJ
,
Hansell
DM
.
CT findings in bronchiectasis: limited value in distinguishing between idiopathic and specific types
.
AJR Am J Roentgenol
.
1995
;
165
(
2
):
261
7
. .
18.
Padilla-Galo
A
,
Olveira
C
,
Fernández de Rota-Garcia
L
,
Marco-Galve
I
,
Plata
AJ
,
Alvarez
A
, et al
Factors associated with bronchiectasis in patients with uncontrolled asthma; the NOPES score: a study in 398 patients
.
Respir Res
.
2018
;
19
(
1
):
43
. .
19.
Coman
I
,
Pola-Bibián
B
,
Barranco
P
,
Vila-Nadal
G
,
Dominguez-Ortega
J
,
Romero
D
, et al
Bronchiectasis in severe asthma: clinical features and outcomes
.
Ann Allergy Asthma Immunol
.
2018
;
120
(
4
):
409
13
. .
20.
Garcia-Clemente
M
,
Enriquez-Rodriguez
AI
,
Iscar-Urrutia
M
,
Escobar-Mallada
B
,
Arias-Guillen
M
,
Lopez-Gonzalez
FJ
, et al
Severe asthma and bronchiectasis
.
J Asthma
.
2019
;
1
5
.
21.
Ulrik
CS
.
Outcome of asthma: longitudinal changes in lung function
.
Eur Respir J
.
1999
;
13
(
4
):
904
18
. .
22.
Dimakou
K
,
Gousiou
A
,
Toumbis
M
,
Kaponi
M
,
Chrysikos
S
,
Thanos
L
, et al
Investigation of bronchiectasis in severe uncontrolled asthma
.
Clin Respir J
.
2018 Mar
;
12
(
3
):
1212
8
. .
23.
Menzies
D
,
Holmes
L
,
McCumesky
G
,
Prys-Picard
C
,
Niven
R
.
Aspergillus sensitization is associated with airflow limitation and bronchiectasis in severe asthma
.
Allergy
.
2011
;
66
(
5
):
679
85
. .
24.
Gupta
S
,
Siddiqui
S
,
Haldar
P
,
Raj
JV
,
Entwisle
JJ
,
Wardlaw
AJ
, et al
Qualitative analysis of high-resolution CT scans in severe asthma
.
Chest
.
2009
;
136
(
6
):
1521
8
. .
25.
Ni
Y
,
Shi
G
,
Yu
Y
,
Hao
J
,
Chen
T
,
Song
H
.
Clinical characteristics of patients with chronic obstructive pulmonary disease with comorbid bronchiectasis: a systemic review and meta-analysis
.
Int J Chron Obstruct Pulmon Dis
.
2015
;
10
:
1465
75
. .
26.
Du
Q
,
Jin
J
,
Liu
X
,
Sun
Y
.
Bronchiectasis as a comorbidity of chronic obstructive pulmonary disease: a systematic review and meta-analysis
.
PLoS One
.
2016
;
11
(
3
):
e0150532
. .
27.
Harmanci
E
,
Kebapci
M
,
Metintas
M
,
Ozkan
R
.
High-resolution computed tomography findings are correlated with disease severity in asthma
.
Respiration
.
2002
;
69
(
5
):
420
6
. .
28.
Gao
YH
,
Guan
WJ
,
Liu
SX
,
Wang
L
,
Cui
JJ
,
Chen
RC
, et al
Aetiology of bronchiectasis in adults: a systematic literature review
.
Respirology
.
2016
;
21
(
8
):
1376
83
. .
29.
Stolz
D
,
Barandun
J
,
Borer
H
,
Bridevaux
PO
,
Brun
P
,
Brutsche
M
, et al
Diagnosis, prevention and treatment of stable COPD and acute exacerbations of COPD: the Swiss recommendations 2018
.
Respiration
.
2018
;
96
(
4
):
382
98
. .
30.
Mikos
M
,
Grzanka
P
,
Sladek
K
,
Pulka
G
,
Bochenek
G
,
Soja
J
, et al
High-resolution computed tomography evaluation of peripheral airways in asthma patients: comparison of focal and diffuse air trapping
.
Respiration
.
2009
;
77
(
4
):
381
8
. .
31.
Chalmers
JD
,
Hill
AT
.
Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis
.
Mol Immunol
.
2013
;
55
(
1
):
27
34
. .
32.
Agusti
A
,
Bel
E
,
Thomas
M
,
Vogelmeier
C
,
Brusselle
G
,
Holgate
S
, et al
Treatable traits: toward precision medicine of chronic airway diseases
.
Eur Respir J
.
2016
;
47
(
2
):
410
9
. .
33.
Richards
LB
,
Neerincx
AH
,
van Bragt
JJMH
,
Sterk
PJ
,
Bel
EHD
,
Maitland-van der Zee
AH
.
Biomarkers and asthma management: analysis and potential applications
.
Curr Opin Allergy Clin Immunol
.
2018
;
18
(
2
):
96
108
. .
34.
Bagnasco
D
,
Ferrando
M
,
Varricchi
G
,
Passalacqua
G
,
Canonica
GW
.
A critical evaluation of anti-IL-13 and anti-IL-4 strategies in severe asthma
.
Int Arch Allergy Immunol
.
2016
;
170
(
2
):
122
31
. .
35.
Pasteur
MC
,
Bilton
D
,
Hill
AT
.
British thoracic society bronchiectasis non CFGG. British Thoracic Society guideline for non-CF bronchiectasis
.
Thorax
.
2010
;
65
(
Suppl 1
):
i1
58
.
36.
O’Neill
S
,
Sweeney
J
,
Patterson
CC
,
Menzies-Gow
A
,
Niven
R
,
Mansur
AH
, et al
The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry
.
Thorax
.
2015
;
70
(
4
):
376
8
. .
37.
Goeminne
PC
,
Vanfleteren
LEGW
.
Bronchiectasis economics: spend money to save money
.
Respiration
.
2018
;
96
(
5
):
399
402
. .
38.
Chalmers
JD
,
Goeminne
P
,
Aliberti
S
,
McDonnell
MJ
,
Lonni
S
,
Davidson
J
, et al
The bronchiectasis severity index. An international derivation and validation study
.
Am J Respir Crit Care Med
.
2014
;
189
(
5
):
576
85
. .
39.
Martinez-Garcia
MA
,
de Gracia
J
,
Vendrell Relat
M
,
Giron
RM
,
Maiz Carro
L
,
de la Rosa Carrillo
D
, et al
Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score
.
Eur Respir J
.
2014
;
43
(
5
):
1357
67
.
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