FENOTIPAREA BRONSIECTAZIILOR

Sel lucrari Dr.Nicoleta Bertici

Departamentul Pneumologie, UMF “Victor Babes” Timisoara

In 1950 Reid facea prima clasificare a bronsiectaziilor: cilindrice,
cistice si varicoase…..
 Astazi vorbim de fenotiparea
bronsiectaziilor…

• A phenotype (from Greek phainein, meaning "to show", and typos, meaning
"type") is the composite of an organism's observable characteristics or traits,
such as its morphology, development, biochemical or physiological
properties, phenology, behavior, and products of behavior.

• A phenotype results from the expression of an organism's genes as well as

the influence of environmental factors and the interactions between the two

• genotype (G) + environment (E) → phenotype (P)

The clinical presentation and prognosis of non-cystic fibrosis bronchiectasis are
both very heterogeneous.

Ken we to identify different clinical phenotypes for non-cystic fibrosis

bronchiectasis and their impact on prognosis ?
Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis
Ravishankar Chandrasekaran et all, BMC Pulm Med. 2018; 18: 83. Published online 2018 May 22.
Metaanaliza
2000/ 2012
2013
2012/
2013 Prevalence of bronchiectasis in four European countries (I)
Marc Miravitlles 1, Mònica Monteagudo 2, Teresa Rodríguez 2, Miriam Barrecheguren 1, Pere Simonet 3, María
E. Sáez 4, Antonio González-Pérez 4, Luis A. García Rodríguez 4, Juha Mehtälä 5, Ilona Iso-Mustajärvi 5,
Sebastian Braun 6, Jennifer Haas 6, Felix C. Ringshausen 7, Fabian Juelich 8, Gisela Korfmann 8, and Kiliana
Suzart-Woischnik 9,*

• Background: Bronchiectasis is a pulmonary disorder defined morphologically as permanent

bronchial dilatation involving a vicious cycle of recurrent infection, inflammation and bronchial-
wall damage. Despite its clinical importance, there is a lack of robust prevalence estimates of
bronchiectasis especially for Europe.
• Objectives: The primary objective of this research project was to estimate the prevalence of
bronchiectasis not associated with cystic fibrosis in four European countries (Germany, Spain,
Sweden and the United Kingdom [UK]). Furthermore, patient demographics and the clinical
burden of illness were characterized.
• Methods: Four observational studies were conducted using administrative databases. The
study period included the calendar year 2013 in Germany and 2012 in the other three
countries. Bronchiectasis subjects were identified via International Classification of Diseases
(ICD, 9th or 10th revision) Codes or Read Codes, as applicable. Data on healthcare resource
utilization were analysed to characterize the clinical burden of illness. Descriptive statistics
were performed.
Prevalence of bronchiectasis in four European countries (II)
 Prevalence of bronchiectasis in four European countries (III)
Marc Miravitlles et all

Conclusions

• In Europe, bronchiectasis is a rarely

documented disease with a broad range of
prevalence estimates in different countries.
However, it is unclear whether these ranges
can be attributed to geographic differences or
different coding behaviour.

• Overall, the documented health resource

utilization indicates a high disease burden.
2006/
Lobar Distribution in Non-Cystic Fibrosis Bronchiectasis Predicts
2014 Bacteriologic Pathogen Treatment (I)
Shimon Izhakian 1 , Walter Wasser 2 , Leonardo Fuks 1 , Baruch Vainshelboim 1 , Benjamin Fox 1 , Oren Fruchter 1 , and Mordechai Kramer 1 1
Rabin Medical Center, Beilinson Hospital Petach Tikva, 49100 Israel. 2 and Rambam Health Care Campus, Haifa, Israel

• Purpose: Non-cystic fibrosis bronchiectasis (NCFBr) is a major cause of morbidity

due to frequent infectious exacerbations. We analyzed the influence of patient age
and bronchiectasis location on the bacterial profile of patients with NCFBr.

• Methods: This retrospective cohort study included 339 subjects diagnosed with an
infectious exacerbation of NCFBr during the 9-year period between January 2006
and December 2014. Bronchoalveolar lavage (BAL) cultures and highresolution
computed tomography scans (HRCT) were utilized to characterize the location of
the bronchiectasis and bacteriologic pathogenic profile.
Lobar Distribution in Non-Cystic Fibrosis Bronchiectasis Predicts
Bacteriologic Pathogen Treatment (II)
 Lobar Distribution in Non-Cystic Fibrosis Bronchiectasis Predicts
Bacteriologic Pathogen Treatment (III)
Shimon Izhakian 1 , Walter Wasser 2 , Leonardo Fuks 1 , Baruch Vainshelboim 1 , Benjamin Fox 1 , Oren Fruchter 1 , and Mordechai Kramer 1
1 Rabin Medical Center, Beilinson Hospital Petach Tikva, 49100 Israel. 2 and Rambam Health Care Campus, Haifa, Israel

Conclusions:
• H. influenzae was more prevalent in younger patients

• P. aeruginosa, Enterobacteriaceae and NTM

predominated in older patients.

• Different pathogens were associated with different

lobar distributions. The RML, RLL and LLL showed a
greater tendency to develop bronchiectasis than
other lobes.
 The Bronchiectasis Severity Index. An International Derivation and
2008/
2012 Validation Study / BSI index
James D. Chalmers1, Pieter Goeminne2, Stefano Aliberti3, Melissa
J. McDonnell4,5, Sara Lonni3, John Davidson4, Lucy Poppelwell1, Waleed Salih1, Alberto Pesci3, Lieven J. Dupont2, Thomas
C. Fardon1, Anthony De Soyza4,5, and Adam T.Hill6

• Rationale: There are no risk stratification tools for morbidity and mortality in
bronchiectasis. Identifying patients at risk of exacerbations, hospital admissions, and
mortality is vital for future research.

• Objectives: This study describes the derivation and validation of the Bronchiectasis
Severity Index (BSI).

• Methods: Derivation of the BSI used data from a prospective cohort study
(Edinburgh, UK, 2008–2012) enrolling 608 patients. Cox proportional hazard
regression was used to identify independent predictors of mortality and
hospitalization over 4-year follow-up. The score was validated in independent
cohorts from Dundee, UK (n = 218); Leuven, Belgium (n = 253); Monza, Italy (n =
105); and Newcastle, UK (n = 126).
 The Bronchiectasis Severity Index. An International Derivation
and Validation Study / BSI index
James D. Chalmers1, Pieter Goeminne2, Stefano Aliberti3, Melissa
J. McDonnell4,5, Sara Lonni3, JohnDavidson4, Lucy Poppelwell1, Waleed Salih1, Alberto Pesci3, Lieven J. Dupont2, Thomas
C. Fardon1, Anthony De Soyza4,5, and Adam T.Hill6

• Measurements and Main Results: Independent predictors of future hospitalization

were prior hospital admissions,
– Medical Research Council dyspnea score greater than or equal to 4,
– FEV1 < 30% predicted, Pseudomonas aeruginosa colonization,
– colonization with other pathogenic organisms, and
– three or more lobes involved on high-resolution computed tomography.
• Independent predictors of mortality were older age, low FEV1, lower body mass
index, prior hospitalization, and three or more exacerbations in the year before the
study.
• The derived BSI predicted mortality and hospitalization: area under the receiver
operator characteristic curve (AUC) 0.80 (95% confidence interval, 0.74–0.86) for
mortality and AUC 0.88 (95% confidence interval, 0.84–0.91) for hospitalization,
respectively. There was a clear difference in exacerbation frequency and quality of life
using the St. George’s Respiratory Questionnaire between patients classified as low,
intermediate, and high risk by the score (P < 0.0001 for all comparisons). In the
validation cohorts, the AUC for mortality ranged from 0.81 to 0.84 and for
hospitalization from 0.80 to 0.88.

• Conclusions: The BSI is a useful clinical predictive tool that identifies patients at risk of
future mortality, hospitalization, and exacerbations across healthcare systems.
Read More: http://www.atsjournals.org/doi/abs/10.1164/rccm.201309-1575OC#.V-L8CPl95dg
 Online Calculation Tool
Enter your patient’s information to calculate the Bronchiectasis Severity Index
• Age
• BMI
• % FEV1 Predicted
• Previous Hospital AdmissionHas the patient been hospitalised with a severe exacerbation in the past 2 years?
• Number of exacerbations in previous year
• MRC Breathlessness ScoreMRC Breathlessness
• Pseudomonas ColonisationChronic colonisation is defined by the isolation of pseudomonas aeriginosa in
sputum culture on 2 or more occasions, at least 3 months apart in a 1 year period
• Colonisation with other organismsChronic colonisation is defined by the isolation of potentially pathogenic
bacteria in sputum culture on 2 or more occasions, at least 3 months apart in a 1 year period.
• Radiological Severity

• Bronchiectasis Severity Score

– 0-4Mild Bronchiectasis
1 year outcomes: 0 - 2.8 % mortality rate, 0 - 3.4 % hospitalisation rate
4 year outcomes: 0 - 5.3 % mortality rate, 0 - 9.2 % hospitalisation rate
– 5 - 8Moderate Bronchiectasis
1 year outcomes: 0.8 - 4.8 % mortality rate, 1.0 - 7.2 % hospitalisation rate
4 year outcomes: 4 % - 11.3 % mortality rate, 9.9 - 19.4 % hospitalisation rate
– 9 +Severe Bronchiectasis
1 year outcomes: 7.6 % - 10.5 % mortality rate, 16.7 - 52.6 % hospitalisation rate
4 year outcomes: 9.9 - 29.2 % mortality, 41.2 - 80.4 % hospitalisation rate
2014

Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score

Miguel Á. Martínez-García, Javier de Gracia, Monserrat Vendrell Relat, Rosa-Maria Girón, Luis Máiz Carro, David de la Rosa Carrillo,
Casilda Olveira

Abstract
• Bronchiectasis is a multidimensional disease and, therefore, its severity or prognosis cannot be
adequately quantified by analysing one single variable. The objective of the present study was to
develop a multidimensional score that classifies the severity of bronchiectasis according to its
prognosis.

• This is an observational multicentre study including 819 patients diagnosed with non-cystic fibrosis
bronchiectasis using high-resolution computed tomography. 397 subjects were selected at random to
construct the score while the remaining 422 were used for its validation. The outcome was 5-year all-
cause mortality after radiological diagnosis. A logistic regression analysis was used to select the
variables included in the final score.

• The final seven-point score incorporated five dichotomised variables: forced expiratory volume in 1 s
% predicted (F, cut-off 50%, maximum value 2 points); age (A, cut-off 70 years, maximum value 2
points); presence of chronic colonisation by Pseudomonas aeruginosa (C, dichotomic, maximum
value 1 point); radiological extension (E, number of lobes affected, cut-off two lobes, maximum value
1 point); and dyspnoea (D, cut-off grade II on the Medical Research Council scale, maximum value 1
point) to construct the FACED score. The validation cohort confirmed the score’s validity.

• We conclude that this easy-to-use multidimensional grading system proved capable of accurately
classifying the severity of bronchiectasis according to its prognosis.

European Respiratory Journal 2014 43: 1357-1367;

 The FACED score uses the following
criteria:
• F – FEV1 (> 50% = 0 points, ≤ 50% = 2 points)
• A – Age (≤ 70 years = 0 points, > 70 years = 2 points)
• C – Chronic colonisation (no Pseudomonas = 0 points,
presence of Pseudomonas = 1 point)
• E – Extension (1 lobe = 1 point, ≥ 2 = 2 points)
• D – Dyspnoea (no dyspnoea = 0 points, ≥ 2 on Medical
Research Council scale = 1 point)

Scoring:
• 0-2 points Mild bronchiectasis
• 3-4 points Moderate bronchiectasis
• 5-7 points Severe bronchiectasis
2016 Clinical phenotypes in adult patients with bronchiectasis(I)
Aliberti S1, Lonni S2, Dore S3, McDonnell MJ4, Goeminne PC5, Dimakou K6, Fardon
TC7, Rutherford R4, Pesci A2, Restrepo MI8, Sotgiu G3, Chalmers JD7.

• Bronchiectasis is a heterogeneous disease. This study aimed at

identifying discrete groups of patients with different clinical and
biological characteristics and long-term outcomes.
• This was a secondary analysis of five European databases of
prospectively enrolled adult outpatients with bronchiectasis.
• Principal component and cluster analyses were performed using
demographics, comorbidities, and clinical, radiological, functional and
microbiological variables collected during the stable state.
• Exacerbations, hospitalisations and mortality during a 3-year follow-up
were recorded.
• Clusters were externally validated in an independent cohort of patients
with bronchiectasis, also investigating inflammatory markers in sputum.

Eur Respir J. 2016 Apr;47(4):1113-22. doi: 10.1183/13993003.01899-2015. Epub 2016 Feb 4.

 Clinical phenotypes in adult patients with bronchiectasis(II)
Aliberti S1, Lonni S2, Dore S3, McDonnell MJ4, Goeminne PC5, Dimakou
K6, Fardon TC7, Rutherford R4, Pesci A2, Restrepo MI8, Sotgiu G3, Chalmers JD7.

• Among 1145 patients, median age 66 years; 40% male

• four clusters were identified driven by
– the presence of chronic infection with Pseudomonas aerug -16%
– other chronic infection" - 24%
– daily sputum – 33%
– “dry bronchiectasis“ – 27%.
• Patients in the four clusters showed significant differences in terms of
quality of life, exacerbations, hospitalisations and mortality during
follow-up.
• In the validation cohort, free neutrophil elastase activity,
myeloperoxidase activity and interleukin-1β levels in sputum were
significantly different among the clusters.
• Identification of four clinical phenotypes in bronchiectasis could favour
focused treatments in future interventional studies designed to alter
the natural history of the disease.
Clinical phenotypes in adult patients with bronchiectasis (III)
2016

The Multiple Faces of Non-Cystic Fibrosis Bronchiectasis. A Cluster Analysis Approach(I)

Martínez-García MÁ1, Vendrell M2,3, Girón R4, Máiz-Carro L5, de la Rosa Carrillo D6, de Gracia J3,7, Olveira C8.

RATIONALE:
The clinical presentation and prognosis of non-cystic fibrosis bronchiectasis are both very
heterogeneous.
OBJECTIVES:
To identify different clinical phenotypes for non-cystic fibrosis bronchiectasis and their impact on
prognosis.
METHODS:
Using a standardized protocol, we conducted a multicenter observational cohort study at six Spanish
centers with patients diagnosed with non-cystic fibrosis bronchiectasis before December 31, 2005,
with a 5-year follow-up from the bronchiectasis diagnosis. A cluster analysis was used to classify the
patients into homogeneous groups by means of significant variables corresponding to different
aspects of bronchiectasis (clinical phenotypes): age, sex, body mass index, smoking habit, dyspnea,
macroscopic appearance of sputum, number of exacerbations, chronic colonization with
Pseudomonas aeruginosa, FEV1, number of pulmonary lobes affected, idiopathic bronchiectasis, and
associated chronic obstructive pulmonary disease. Survival analysis (Kaplan-Meier method and log-
rank test) was used to evaluate the comparative survival of the different subgroups.

Ann Am Thorac Soc. 2016 Sep;13(9):1468-75. doi: 10.1513/AnnalsATS.201510-678OC

The Multiple Faces of Non-Cystic Fibrosis Bronchiectasis. A Cluster Analysis Approach(II)
Martínez-García MÁ1, Vendrell M2,3, Girón R4, Máiz-Carro L5, de la Rosa Carrillo D6, de Gracia J3,7, Olveira C8.

MEASUREMENTS AND MAIN RESULTS:

A total of 468 patients with a mean age of 63 (15.9) years were analyzed. Of these, 58% were
females, 39.7% had idiopathic bronchiectasis, and 29.3% presented with chronic Pseudomonas
aeruginosa colonization. Cluster analysis showed four clinical phenotypes:
(1) younger women with mild disease,
(2) older women with mild disease,
(3) older patients with severe disease who had frequent exacerbations, and
(4) older patients with severe disease who did not have frequent exacerbations.

The follow-up period was 54 months, during which there were 95 deaths. Mortality was low in the
first and second groups (3.9% and 7.6%, respectively) and high for the third (37%) and fourth
(40.8%) groups. The third cluster had a higher proportion of respiratory deaths than the fourth
(77.8% vs. 34.4%; P < 0.001).
CONCLUSIONS:
Using cluster analysis, it is possible to separate patients with bronchiectasis into distinct clinical
phenotypes with different prognoses.
 2016
Characterization of bronchiectasis in the elderly
Giuseppe Bellelli 1, James D Chalmers 2, Giovanni Sotgiu 3, Simone Dore 3, Melissa J McDonnell 4, Pieter C
Goeminne 5, Katerina Dimakou 6, Dusan Skrbic 7, Andrea Lombi 8, Federico Pane 8, Dusanka Obradovic 7,
Thomas C Fardon 2, Robert M Rutherford 4, Alberto Pesci 8, and Stefano Aliberti 8,*

• Although bronchiectasis particularly affects people ≥65 years of age, data describing clinical
characteristics of the disease in this population are lacking. This study aimed at evaluating
bronchiectasis features in older adults and elderly, along with their clinical outcomes.
• Methods. This was a secondary analysis of six European databases of prospectively enrolled
adult outpatients with bronchiectasis. Bronchiectasis characteristics were compared across
three study groups: younger adults (18-65 years), older adults (66-75 years), and elderly
(and >76 years). 3-year mortality was the primary study outcome.
• Results: Among 1,258 patients enrolled (median age: 66 years; 42.5% males), 50.9% were
>65 years and 19.1 >75 years old. Elderly patients were more comorbid, had worse quality of
life and died more frequently than the others. Differences were detected among the three
study groups with regard to neither the etiology nor the severity of bronchiectasis, nor the
prevalence of chronic infection with P. aeruginosa. In multivariate regression model, age,
low BMI, previous hospitalizations, low FEV1 and COPD were
independent predictors of 3-year mortality, after adjustment for covariates.
• Conclusions: Bronchiectasis does not substantially differ across age groups. Poor outcomes
in elderly patients with bronchiectasis might be directly related to individual’s frailty that
should be further investigated in clinical studies.
Figure 2: Prevention of exacerbations in stable patients with bronchiectasis Exacerbations of bronchiectasis in adults

Margarida T Redondo1, Sebastian Ferri2, James D Chalmers3

2016
Quality of life as an outcome measure in clinical trials
Alexandra Quittner, Miami College of Arts and Science, USA
1st World Bronchiectasis Conference, Hannover 2016

• TheQualityofLife-Bronchiectasis(QOL-B), is a new, self-administered, patient-

reported outcome measure assessing symptoms, functioning and health-related
quality of life for patients with non-cystic fibrosis (CF) bronchiectasis.
• It was developed using the FDA Guidance on Patient-Reported Outcomes (FDA, 2009)
and with consultations from the FDA. Thus, it can be used as a primary or secondary
endpoint in clinical trials of new medications.
• It contains 37 items on 8 scales (Respiratory Symptoms, Physical, Role, Emotional and
Social Functioning, Vitality, Health Perceptions and Treatment Burden).
• Psychometric analyses of the QOL-B V.3.0 indicated is has excellent internal
consistency (Cronbach’s α ≥0.70) and 2-week test–retest reliability (intraclass
correlation coefficients ≥0.72), as well as convergent validity with the 6 min walk test
and the SGRQ. It has demonstrated good discriminant validity between patients,
based on baseline FEV1% predicted.
• The QOL-B has been translated into over 40 languages and is being utilized in several
international clinical trials.
2017 European Respiratory Society
guidelines for the management
of adult bronchiectasis
• Chronic airways infection, most frequently with Haemophilus
influenzae and Pseudomonas aeruginosa and less frequently with
Moraxella catarrhalis, Staphylococcus aureus and
Enterobacteriaceae, stimulate and sustain lung inflammation.
• Persistent isolation of these organisms in sputum or bronchoalveolar
lavage is associated with an increased frequency of exacerbations,
worse quality of life and increased mortality.

• This is particularly the case with P. aeruginosa infection. A systematic

review of observational studies identified that P. aeruginosa infection
is associated with a three-fold increase in mortality risk, an almost
seven-fold increase in risk of hospital admission and an average of
one additional exacerbation per patient per year.

Polverino E, Goeminne PC, McDonnell MJ, et al. European Respiratory Society guidelines for the management of adult
bronchiectasis. Eur Respir J 2017; 50: 1700629 [https://doi.org/ 10.1183/13993003.00629-2017].
Noi studii – microbiomul
 Differences in the microbiome
between Europe, the US and the
Asia-Pacific by sputum culture
illustrating the predominant
organisms in stable states and
viruses only during exacerbations.
The bacteriome contributes to host
inflammation and disease severity,
the virome in exacerbations and the
mycobiome is an understudied
group with potential clinical impact.

Abbreviations: US – United States,

UK – United Kingdom, P. aeruginosa
– Pseudomonas aeruginosa, NTM –
Non-Tuberculosis Mycobacteria,
H.influenzae – Haemophilus
influenzae, NTHi – Non-typeable
Haemophilus influenzae, HTLV-1 –
Human T-Lymphotropic Virus type
1, C. albicans – Candida albicans,
ABPA – Allergic Broncho-Pulmonary
Aspergillosis, CPA – Chronic
Pulmonary Aspergillosis, IPA –
Invasive Pulmonary Aspergillosis, IA
– Invasive Aspergillosis ↑ -
Increased, ↓ - Decreased
Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis
Ravishankar Chandrasekaran et all, BMC Pulm Med. 2018; 18: 83. Published online 2018 May 22.
Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis
Ravishankar Chandrasekaran et all, BMC Pulm Med. 2018; 18: 83. Published online 2018 May 22.
Next level

Se va ajunge la nivel de individ sa-si cunoasca “harta ” microbiomului propriu?!

 Concluzii
• Exista fenotipuri distincte care trebuiesc cunoscute si abordate diferit.

• Evaluarea severitatii bronsiectaziilor nu trebuie sa ramana exclusiv la

judecata subiectiva a clinicienilor; acestia trebuie sa trateze in acord
cu gravitatea situatiei apeland la sisteme specifice multidimensionale
cum sunt FACED si/sau BSI.

• Majoritatea clinicienilor sunt preocupati de tratatrea pacientilor in

exacerbare, dar este important sa nu ignoram pacientii in perioadele
stabile - care necesita mult mai multa atentie.

• Avem la dispozitie ghiduri specifice de tratament (ghidul spaniol

SEPAR 2008, British Thoracic Society guideline on bronchiectasis 2010,
si recent ghidul ERS 2017) .
 Discutii / Intrebari?
• Ce facem cu pacienti asimptomatici, fara
leziuni radiologice evidente dar cu germeni
patogeni prezenti constant in sputa?

• Ce facem cu pacientii cu germeni multidrog

rezistenti ?
• Bronchiectasis is a common chronic respiratory disease presenting with cough,
sputum production, respiratory infections, and impaired QoL. The cause is unknown
in a majority of cases and the management remains largely empirical due to the
absence of large-scale clinical trials.

The exact prevalence is not known, but recent estimates of prevalence are
67/100,000 in Germany and 485/100,000 in men and 566/100,000 in women in the
UK.
Extrapolating this to the European Union as a whole, we might expect at least
350,000 patients with bronchiectasis in the EU, increasing to 2,500,000 patients if the
data from the UK are generalizable across Europe. This compares to approximately
70,000 patients with cystic fibrosis (CF) worldwide and an incidence of COPD of
approximately 7% in Europe. Consequently, it might be estimated that there are 15-
100 cases of COPD for every case of bronchiectasis.

Although bronchiectasis has historically been a neglected disease, a resurgence in

interest in the disease over the past several years has generated a volume of new
evidence that improves our understanding of the disease. Exacerbations of
bronchiectasis account for a large proportion of the clinical workload and the
economic impact of bronchiectasis on health care systems internationally.

Margarida T Redondo1, Sebastian Ferri2, James D Chalmers3

Date of Web Publication29-Jun-2016
Margarida T Redondo1, Sebastian Ferri2, James D Chalmers3
 PROGNOSIS - the German Bronchiectasis Registry
Felix C. Ringshausen 1,* , Andrés de Roux 2, Roland Diel 3, Grit Barten 4, Annegret Zurawski 5, Tobias Welte 1,
and Jessica Rademacher 6

• While bronchiectasis is the hallmark of CF lung manifestation, there is still no approved pharmacotherapy
available for the treatment of bronchiectasis not associated with CF.
• Consequently, bronchiectasis is considered one of the most neglected diseases in respiratory medicine, with a
great lack of research and an urgent need to determine the optimal management strategies.
• Recently, we provided first epidemiological evidence on the burden and the prevalence of bronchiectasis in
Germany, clearly demonstrating that bronchiectasis is not an orphan disease and that it is associated with
increasing healthcare unsafe
• In order to advance research in the field of bronchiectasis we proposed the German Bronchiectasis Registry
PROGNOSIS, which is aligned and collaborating with EMBARC, the European Bronchiectasis Registry.
• The main objectives of PROGNOSIS are:
– To sustain and expand a national, representative, prospective, observational and longitudinal
bronchiectasis database, recruiting a minimum of 750 patients from 25-35 centers from all levels of
healthcare across Germany over a 3-year period
– To study the epidemiology of bronchiectasis and to provide an estimate of the distribution of
bronchiectasis etiologies across different levels of healthcare
– To provide real-life data regarding the current management of bronchiectasis
– To perform observational research into bronchiectasis, particularly in areas where single center datasets
are underpowered, such as in rare etiologies or determining markers of prognosis
– To promote collaborative clinical, basic and translational research in bronchiectasis
– To provide a registry of well phenotypes patients with bronchiectasis in clinical centers potentially eligible
for enrollment into future clinical trials.
• Currently, after having started recruitment in summer 2015 PROGNOSIS is well inline with the projected
milestone of 250 recruited patients within the first year, with 30 centers actively participating.
Figure 1: Management of acute exacerbations of bronchiectasis

Exacerbations of bronchiectasis in adults

Margarida T Redondo1, Sebastian Ferri2, James D Chalmers3

A few evidence-based treatments are available for the prevention and the management of
bronchiectasis exacerbations: Exacerbations of bronchiectasis in adults

Margarida T Redondo1, Sebastian Ferri2, James D Chalmers3

Vaccination (influenza and pneumococcal) is recommended in bronchiectasis patients by the

BTS and Spanish Society of Pneumology and Thoracic Surgery although there is no evidence
that vaccination reduces the exacerbation rate

Macrolide antibiotics are said to have anti-inflammatory and immunomodulatory properties

in addition to their antibacterial properties. Three placebo-controlled randomized trials
(EMBRACE, BAT, BLESS) show a significant decrease in event-based exacerbation rate and
increase in time to the first exacerbation compared with placebo. Benefits of macrolide
treatment come with a considerable increase in macrolide-resistant pathogens and other
side effects which demand judicious use of long-term macrolide therapy
Intermittent IV antibiotic treatment: In patients with frequent exacerbations despite
prophylactic antibiotics and optimized treatments, 6-8 weekly IV antibiotic therapy has been
shown to reduce exacerbations and improve QoL. [50]

Inhaled antibiotics are commonly used in CF bronchiectasis treatment to

suppress P. aeruginosa and other pathogens. Despite the effectiveness of treatment with
inhaled antibiotics in patients with CF has been demonstrated in several clinical trials,
currently, there are insufficient large studies of patients with non-CF bronchiectasis and most
of them are conflicting. [51],[52],[53]
Most of the randomized clinical trials evaluate inhaled antimicrobial agents included
bronchiectasis patients colonized with P. aeruginosa and used different types of antibiotics
(colistin, tobramycin, gentamicin, or ciprofloxacin). Three distinct trials using aztreonam,
gentamicin, and ciprofloxacin, which did not specifically require P. aeruginosa colonization
for inclusion, demonstrated bacterial load reduction in the airways, but this effect does not
correspond with improvement in clinical endpoints. [12]
The largest trial (n = 500) of inhaled aztreonam in bronchiectasis patients -85% of whom
were P. aeruginosa colonized - failed to demonstrate reduced exacerbation rates or improved
QoL. Other authors report prolonged time to exacerbation and improved health-related
QoL. [51]Nevertheless, inhaled antibiotics are widely used in clinical practice and appear to
have benefits in selected patients. The main adverse effect is bronchospasm
Targeted antibiotics: Trials of long-term penicillins and tetracyclines from the 1980's or
earlier suggest benefits in patients with bronchiectasis, but further studies are
needed. [54] Long-term penicillins and tetracyclines are used either as alternatives in patients
with macrolide intolerance or for targeted treatment of specific pathogens

Airway clearance techniques are recommended for patients with stable bronchiectasis to
optimize the airway clearance leading to decrease sputum expectoration, symptoms, and
exacerbation rate and also increase lung function, gas exchange, and QoL.
Specific techniques used in airway clearance include:
Breathing exercises such as the active cycle of breathing technique
Gravity-assisted drainage
Autogenic drainage
Manual techniques such as clapping
Forced expiratory technique
Application of positive expiratory pressure devices
Adherence is a major problem, particularly when patients feel well, and hence, it
is important to tailor the techniques to the patient's lifestyle, to emphasize the
importance of airway clearance at each visit, and to discuss adherence [56]
Hypertonic saline (HTS) 4-7% is reported to improve hydration of the airway
surface and the rheology and transportability of sputum. Inhalation of HTS has
short-term positive effects on airways clearance in bronchiectasis; however, its
long-term effects are unknown. One trial showed no benefits compared to
isotonic saline over 12 months [57]

Pulmonary rehabilitation: Lee et al. showed a reduction in exacerbations over 12

months in patients randomized to exercise training, suggesting that pulmonary
rehabilitation may play a role in reducing exacerbations. [58] All patients with
significant breathlessness should be considered for exercise treatments.
 Definitia exacerbarii
The British Thoracic Society

• the deterioration of at least three respiratory

symptoms (cough, increased sputum
production, volume, purulence or change in
viscosity with or without increasing wheeze,
increased dyspnea, hemoptysis, and chest pain)
for >24 h and/or systemic complaints, such as
fever, and alterations in chest radiograph.

• Un pacient are in medie 2 exacerbari/an

 Antibiotic use in treatment of non-CF Bronchiectasis: A
retrospective analysis
Mohummad Shaan Goonoo 1,* , Safina Kausar 1 , and Saifudin Khalid 1 1 East Lancashire Hospitals NHS Trust

• Background: The British Thoracic Society (BTS) guidelines recommend

obtaining sputum cultures when patients are stable and before
administering antibiotics during an exacerbation of bronchiectasis.
Additionally, criteria are described for Outpatient Parenteral Antibiotic
Therapy (OPAT) services use.
• Aims: To assess use of antibiotics, ensure we are following BTS and trust
guidelines and evaluate OPAT services use.
• Materials and Methods: A retrospective review of patients, admitted with
acute exacerbation of non-cystic fibrosis bronchiectasis between August
2014 and August 2015, was done using clinical coding (n=58). The
following were compared to guidelines: sputum bacteriology culture, use
of empirical antibiotics, involvement of microbiologists, objective
evaluation of parenteral antibiotics and OPAT services use.
 Antibiotic use in treatment of non-CF Bronchiectasis: A retrospective analysis
Mohummad Shaan Goonoo 1,* , Safina Kausar 1 , and Saifudin Khalid 1 1 East
Lancashire Hospitals NHS Trust

• Results: 55% had sputum sent for culture and sensitivity (C&S) by their General
Practitioner when stable. 83% had no sputum sent for C&S on admission before
starting antibiotics. Microbiology discussion took place in only 7 cases. 12 patients’
sputum grew pseudomonas species. Out of 20 patients receiving IV antibiotics for
more than 3 days, 65% received Piperacillin/Tazobactam. Most patients were
evaluated using CRP measurements but none had spirometry. Only 3 patients were
provided with OPAT services.

• Discussion: Discussion with microbiologists and attempts at objectively measuring

response to parenteral antibiotics were inadequate. OPAT services were not always
provided to patients appearing to be eligible for them; reasons for this were
unclear. One explanation might be that antibiotics which require administration
three times a day are often prescribed while local OPAT services currently only
cater for up to twice daily administration.

• Conclusions: Management of acute exacerbations was often not in line with

guidelines. This can potentially result in lack of antibiotic efficacy or antibiotic
resistance. We suggest greater involvement of microbiologists and using C&S to aid
antimicrobial selection