PULMONARY, SLEEP, AND

CRITICAL CARE UPDATE

Update in Bronchiectasis 2014

Bravein Amalakuhan1, Diego J. Maselli1, and Miguel A. Martinez-Garcia2
1
Division of Pulmonary Diseases/Critical Care Medicine, Department of Medicine, University of Texas Health Science Center and Audie L.
Murphy Division, South Texas Veterans Health Care System, San Antonio, Texas; and 2Pneumology Service, University and Polytechnic
La Fe Hospital, Valencia, Spain

Bronchiectasis, the permanent dilation of one
or more bronchi, is not uncommon, despite
being previously considered an “orphan”
disease. With the widespread use of
computed tomography (CT) of the chest, the
detection of bronchiectasis has become more
frequent and better characterized. Patients
with this disease often have poor quality of
life (QOL), increased health care use, and
poor outcomes. For these reasons there has
been renewed interest in this disease, and in
particular non–cystic fibrosis bronchiectasis
(NCFB). The year 2014 was of particular
importance regarding developments in the
field of NCFB. Significant advances in 2014
included new details on its epidemiology and
pathophysiology, and new insights into the
role of coexisting conditions in these
patients. Furthermore, a better
understanding of exacerbation triggers and
their impact was gained. Newer tools
evaluating severity and QOL have also been
studied. Several studies examining the
benefits of chronic oral macrolide therapy
and inhaled antibiotics were also performed
with promising results. This review examines
articles published in AJRCCM and other
major journals that have made significant
advances in the field of NCFB in 2014.
Epidemiology and Etiology
Epidemiologic trends in NFCB, both in
children and adults, have continued to
change. This may be due in part to increased
clinician awareness, availability of CT, or
changes in the immunologic/microbiologic
environments. Although the most common
cause of bronchiectasis in children is
cystic fibrosis (CF), the prevalence of NCFB
has increased, especially among children
in developing countries. Brower and
colleagues conducted a systematic review of
12 studies consisting of 989 children, to
determine the frequency of various
etiologies of NCFB (1). An etiology was
identified in 63% of children, with a
previous severe pneumonia of bacterial or
viral etiology and B-cell defects as the most
common disorders identified. In a
longitudinal prospective study that
monitored 93 children with NCFB for
3 years, Redding and colleagues reported
that exacerbations occurred on more than
two occasions in the majority of cases
(74%) (2). It was noted that comprehensive
medical care was associated with a decrease
in exacerbation rates. These findings
further exemplify the importance not only
of identifying NCFB in pediatric patients,
but also of ensuring that they receive close
surveillance. Regarding adults, a 5-year
prospective longitudinal study of 245
patients with NCFB observed a mortality
rate of approximately 20% (3). Of these
deaths, 58% were attributed to a respiratory
cause. Variables independently associated
with increased mortality were age,
coexistence of chronic obstructive
pulmonary disease (COPD), and number of
affected lung lobes.
Pathophysiology
Despite previous studies, the various causes
of NCFB have still not been fully understood,
with up to half of cases remaining
without a known etiology. A study
evaluated a unique genotype–phenotype
in the spectrum of primary ciliary
dyskinesia (PCD). Knowles and
colleagues tested patients with normal
ciliary ultrastructure and nondiagnostic
nasal nitric oxide values, but with
phenotypic features of PCD (4). These
patients were found to have RSPH1
mutations resulting in abnormal ciliary
function (abnormal circular beat pattern).
This mutation was associated with milder
respiratory disease and later onset than
typical PCD cases with actual ciliary
structural defects. These findings show
the potential applicability of genetic testing
for the evaluation of NCFB. As with all
developing assays, cost and technical aspects
of the test may be restricted to the research
arena for now.
Biofilms produced by microorganisms
make eradication difficult because of poor
antibiotic penetration and isolation from
the host’s immune response. The presence
of biofilms has been well documented in
patients with CF-related bronchiectasis.

( Received in original form May 12, 2015; accepted in final form July 22, 2015 )
Author Contributions: B.A.: primary editor and author of the following sections: pathophysiology, etiology, microbiology, exacerbations, airway clearance
therapies, long-term inhaled antibiotics, surgical treatment, future therapies, and other therapies; D.J.M.: coeditor and author of the section on oral macrolide
therapy; M.A.M.-G.: coeditor and author of the following sections: trends, severity/quality-of-life tools, and impact. All authors meet the four ICMJE criteria for
authorship.
Correspondence and requests for reprints should be addressed to Bravein Amalakuhan, M.D., South Texas Veterans Health Care System, Audie L. Murphy
Memorial Veterans Hospital, Pulmonary Diseases Section (5th floor), 7400 Merton Minter Boulevard, San Antonio, TX 78229. E-mail: amalakuhan@uthscsa.edu
Am J Respir Crit Care Med Vol 192, Iss 10, pp 1155–1161, Nov 15, 2015
Copyright © 2015 by the American Thoracic Society
DOI: 10.1164/rccm.201505-0926UP
Internet address: www.atsjournals.org

Pulmonary, Sleep, and Critical Care Update 1155


A study investigating pediatric patients
with NCFB demonstrated the presence of
biofilms in the bronchial lavage of this
patient population as well (5). This study
highlighted the potential role of biofilms in
the pathogenesis of NCFB, with more
studies needed to discover therapies that
can penetrate them and disrupt the vicious
cycle of bacterial colonization,
inflammation, and airway destruction.
Microbiology
The altered architecture of bronchiectatic
airways facilitates the growth of multiple
pathogens. Gram-negative bacteria are
isolated more frequently in patients with
NCFB, with Haemophilus influenzae and
Pseudomonas aeruginosa representing the
majority of identified species. However, up
to 40% of good-quality purulent sputum
samples fail to grow any pathogenic
bacteria (6). Moreover, there may be
additional variation depending on
geographical region and the severity of the
disease. For these reasons, a more accurate
approach to microbiologic testing is
required. Yang and colleagues used a 16S
ribosomal DNA pyrosequencing technique
to detect the predominant pathogenic
organism during exacerbations of NCFB.
They found that it was more effective at
detecting the complex bacterial composition
of a sputum sample, with results obtained
2 days earlier than regular cultures, allowing
for earlier institution of the correct
antibiotic (6). Further validation of this
metagenomic approach to pathogen
identification is needed because it has the
potential to impact outcomes by
identifying the causative organism during
an exacerbation. Although these methods
are promising, they fail to differentiate
between colonization of the airways in
established disease versus a true infection.
Highly sensitive tests may detect the
presence of bacterial genetic material with
unclear clinical significance. Still, these
assays may potentially identify patients at
risk for poor outcomes. For example,
one study evaluated the stratification of
stable patients on the basis of their
bacterial sputum composition (7). They
found that patients with sputum samples
dominated by Pseudomonas aeruginosa
(PA) had a higher frequency of
exacerbation and poorer lung function.
Patients whose samples were dominated
1156 American Journal of Respiratory and Critical Care Medicine Volume 192 Number 10 | November 15 2015
PULMONARY, SLEEP, AND CRITICAL CARE UPDATE
by other organisms, including
Haemophilus influenzae, had fewer
exacerbations and better lung function.
Nontuberculous mycobacteria (NTM)
are opportunistic pathogens that afflict
patients with preexisting lung disease, in
particular those with NCFB. A meta-analysis
by Chu and colleagues found that the
prevalence of NTM infections in patients
with NCFB was nearly 10% (8). This
highlights the need to test patients with
NCFB for NTM infections, but the
prevalence historically has varied globally
depending on the geographic region.
Exacerbations
Pulmonary exacerbations of NCFB are
known to be associated with poor outcomes,
and infections are common causes. Gao and
colleagues published the first prospective
study evaluating the incidence and clinical
impact of viral triggers of pulmonary
exacerbations in adults with NCFB (9).
These researchers discovered that
respiratory viruses were found in nearly
50% of exacerbations, compared with 20%
in the stable state (P , 0.001). The most
common viruses were coronavirus (39%),
rhinovirus (25%), and influenza A/B (25%).
Also, a greater proportion of patients with
virus-positive exacerbations received
intravenous antibiotics. Thus, this
study and a similar one by Kapur and
colleagues in children accentuate the
underappreciation of the impact of viral
pathogens in NCFB exacerbations (10).
An accurate etiological diagnosis may limit
unnecessary antibiotics. Nevertheless, the
coexistence of bacteria with viruses during
exacerbations also must be considered.
Table 1. FACED Score
Variable
FEV1
Age
Chronic colonization by Pseudomonas
Extension (number of involved lobes)
MMRC Dyspnea Scale grade
Definition of abbreviation: MMRC = Modified Medical Research Council.
*Points range from 0 to 7: 0–2, mild; 3–5, moderate; 6–7, severe.
Further prospective studies evaluating the
interactions between bacterial and viral
respiratory pathogens during NCFB
exacerbations are needed.
Evaluating Severity
Evaluating the severity of NCFB on the basis
of clinical, spirometric, and radiographic
features, and creating prognostic tools with
these variables, is increasingly being studied.
The development and refinement of these
tools have far-reaching impacts in assessing
the value of future treatments.
Severity Scores
Two research groups simultaneously
published two multidimensional prognostic
tools in 2014. The FACED score is
composed of FEV 1 , age, chronic
colonization with PA, radiographic
extent of disease, and degree of dyspnea
(Table 1) (11). The Bronchiectasis
Severity Index is a similar tool, but
additionally accounts for frequency
of exacerbations/hospitalizations,
colonization with microorganisms other
than PA, and body mass index (Table 2)
(12). Both scales demonstrate a strong
ability to predict mortality 4–5 years
from the time of diagnosis (area under
the curve, 0.87 and 0.8, respectively).
Furthermore, these scores allow for the
division of bronchiectasis into three
severity classes: mild, moderate, or
severe. The FACED score is less complex
with only 5 variables and 10 items, but
still requires external validation. In
contrast, the Bronchiectasis Severity
Index is more complex (9 variables and
26 items) and requires an online
Values Points*
>50% 0
,50% 2
,70 yr old 0
>70 yr old 2
No 0
Yes 1
1 or 2 lobes 0
.2 lobes 1
0–2 0
3–4 1
PULMONARY, SLEEP, AND CRITICAL CARE UPDATE

Table 2. Bronchiectasis Severity Index bronchiectasis (15). LRTI-VAS showed colleagues (20). They observed that in
excellent validity/reliability and good patients with asthma, the presence of
Severity Marker Points*
correlation with other well-validated QOL bronchiectasis was associated with an
questionnaires for NCFB (St. George increased frequency of exacerbations/
Respiratory Questionnaire, Short Form-36 emergency room visits, and greater use of
Age, yr
,50 0 and Leicester Cough Questionnaire). systemic corticosteroids compared with
50–69 2 Goeminne and colleagues used the Sputum asthmatic control subjects without
70–79 4 Color Chart (SCC) to assess severity in bronchiectasis. Whether these patients
>80 6 63 patients with NCFB (SCC and increasing represent a new asthma phenotype is
BMI
,18.5 2
severity: 1, mucoid; 2, mucopurulent; 3, unknown. On the basis of the findings by
18.5–25 0 purulent) (16). This study demonstrated an Kang and colleagues, patients with asthma
26–29 0 association between purulent-appearing and evidence of bronchiectasis should be
>30 0 sputum and elevated levels of various monitored carefully.
FEV1% predicted inflammatory markers. Furthermore, the SCC
.80% 0
50–80% 1 severity score correlated with severity scores COPD
30–49% 2 of bronchiectasis based on CT imaging. In contrast, the association between
,30% 3 bronchiectasis and COPD has been more
Hospital admissions before study extensively studied. Patients with COPD
No 0
Functional Indexes
Yes 5 Before 2014, clinically meaningful measures with bronchiectasis constitute a subgroup of
Exacerbations before study of exercise capacity in patients with patients with more severe disease and more
0 0 bronchiectasis were not well developed, frequent exacerbations. Gatheral and
1 or 2 0 and specifically the change in walking colleagues confirmed the high prevalence of
>3 2 bronchiectasis (69%) in 406 patients with
MMRC Dyspnea Scale distance that actually constituted a clinical
0 0 improvement was unknown. Lee and COPD admitted for their first exacerbation
2 2 colleagues addressed this issue in a study in between 1998 and 2008 (21). This was likely
3 3 which 37 patients underwent a 6-minute an overestimate both because of selection
Pseudomonas colonization bias and because many may have had
No 0
walk distance test and an incremental shuttle
Yes 3 walk distance test, and then repeated the tests radiographic evidence of bronchiectasis
Colonization with other at 8 weeks (17). They concluded that the related to an acute infection and not
organisms minimal clinically important difference was chronic disease. Regardless, the
No 0 a change of 22.3–24.5 m in the 6-minute radiographic presence of bronchiectasis was
Yes 1 associated with a greater number and
.3 lobes involved or cystic walk distance test and 35–37 m in the
bronchiectasis incremental shuttle walk distance test. duration of exacerbations, and the presence
No 0 The Lung Clearance Index (LCI), of PA and NTM in their sputum. Although
Yes 1 which is a measure of ventilation no impact on mortality was found, these
inhomogeneity and calculated by multiple patients require increased surveillance
Definition of abbreviation: BMI = body mass index;
MMRC = Modified Medical Research Council. breath washouts, has been shown to be a given the effects of bronchiectasis on
*Points range from 0 to 26: 0–4, mild; 5–8, sensitive lung function test in detecting early exacerbation rates and severity.
moderate; .9, severe. lung disease in patients with CF. In 2014,
two research groups independently found Rheumatoid Arthritis
that the LCI was more sensitive than FEV1 The coexistence of rheumatoid arthritis
calculator, but it has been successfully (RA) with bronchiectasis has been
in detecting the radiographic progression of
validated in several European countries. well documented, but the impact of
stable NCFB and subsequent clinical
deterioration (18, 19). Newer studies are bronchiectasis on these patients has been
QOL Questionnaires required to further validate the LCI and its poorly understood. The increased
In 2014, there was increased focus on clinical usefulness. employment of CT scans of the chest has
assessing the impact of bronchiectasis on the underlined the prevalence of RA-related
lives of patients. Quittner and colleagues lung diseases. For example, one study
constructed and validated the Quality of Life Impact on Other Disorders reviewed the potential mechanism of the
Questionnaire-Bronchiectasis (QOL-B) tool link between NCFB and RA, finding that
(13). It consists of 37 items with 8 scales. Asthma lung disease often precedes the development
This questionnaire has been validated since Several studies have reported an increased of RA disease (22). A prospective,
its development and translated into various prevalence of bronchiectasis in patients with multicenter, case-controlled, observational
languages, making it readily available (14). asthma, especially in those with severe study found that there was a significantly
Also in 2014, Altenburg and colleagues asthma, and other phenotypes such as the higher prevalence of positive rheumatoid
validated the Lower Respiratory Tract neutrophilic and nonatopic subgroups. In factor and anti–cyclic citrullinated peptide
Infection-Visual Analog Scale (LRTI-VAS), 2014, the first longitudinal study examining in patients with NCFB compared with
which is a specific questionnaire for rapid the impact of bronchiectasis in the evolution normal control subjects and those with
quantification of symptoms in patients with of asthma was published by Kang and obstructive lung disease (23). Fifty percent

Pulmonary, Sleep, and Critical Care Update 1157


of those patients went on to develop RA
within the next 12 months. Puéchal and
colleagues performed a prospective
family-based cohort study of 137 patients
monitored for 11 years (30 with RA and
bronchiectasis, 25 with RA only, 8 with
bronchiectasis only, and 74 normal
control subjects) (24). Those who had
bronchiectasis (hazard ratio, 8.6), early
onset of bronchiectatic symptoms
(hazard ratio, 15.4), and cystic fibrosis
transmembrane conductance regulator
mutations (hazard ratio, 7.2) had an
increased risk of death compared with
those patients without these characteristics.
The reasons why patients with
bronchiectasis and RA had worse outcomes
is not readily apparent, but it is plausible
that a higher propensity for infections and
potentially a higher degree of inflammation
could explain these findings. Further
research on this association is needed
including the potential benefit of treating
patients with both NCFB and RA with
disease-modifying antirheumatic drugs
even in the absence of overt joint disease.
Cancer
Few studies have evaluated the risk of cancer
in patients with bronchiectasis.
A retrospective cohort study from
Taiwan by Chung and colleagues evaluated
57,000 patients with NCFB and 230,000
control subjects, finding that among those
patients with NCFB there was an increased
incidence of all-cause cancer (odds ratio,
1.46), especially esophageal cancer (odds
ratio, 2.06) and hematologic malignancies
(odds ratio, 2.02), even after adjusting for
age, sex, and other comorbidities (25).
Furthermore, the risk of lung cancer in
these patients increased with age (26).
These findings require further validation.
Treatment
Airway Clearance Therapies
In 2014 there were several studies providing
new insights into the area of airway
clearance therapies for patients with
bronchiectasis. A randomized controlled
trial (RCT) by Bilton and colleagues found
that inhaled mannitol at 400 mg twice daily
for 12 months in patients with NCFB did
not reduce exacerbation rates (27).
However, secondary end-point analyses
revealed an improved time to first
exacerbation and quality of life. This was
1158 American Journal of Respiratory and Critical Care Medicine Volume 192 Number 10 | November 15 2015
PULMONARY, SLEEP, AND CRITICAL CARE UPDATE
consistent with a Cochrane review by Hart
and colleagues, showing similar results
along with decreased number of days on
antibiotics (28). This same review found
that inhaled hypertonic saline had no
significant benefit over isotonic saline.
A Cochrane review of mucolytic
agents by Wilkinson and colleagues
reemphasized the harmful effects of
recombinant DNase in patients with NCFB
(29). Although long-term outcomes are
lacking, these authors also demonstrated
that high doses of bromhexine coupled with
antibiotics improved mucus clearance
compared with placebo (29). Furthermore,
they found that erdosteine when combined
with physiotherapy over a 15-day period
improved spirometry and sputum purulence
compared with physiotherapy alone (29).
Again, further long-term trials are needed to
fully elucidate these benefits.
Oral Macrolide Therapy
There has been increased interest in
macrolides for the treatment of NCFB
because of their antiinflammatory
properties and ability to decrease mucus
production. Illustrating this, Liu and
colleagues showed that in patients with
NCFB, 6 months of therapy with
roxithromycin significantly reduced various
inflammatory markers (30). In another
study, Fouka and colleagues demonstrated
that low-dose clarithromycin decreased
levels of CD41IL-171 cells in peripheral
blood and IL-17 levels in exhaled breath
condensate in patients with NCFB (31).
These studies further add to the growing
evidence that macrolides may modulate
inflammatory patterns in NCFB.
The exact mechanism by which
macrolides decrease mucus production
has not been fully elucidated, but
azithromycin has been shown to attenuate
MUC5AC and MUC2 gene expression,
thereby suppressing the synthesis of mucin
on human airway epithelial cells (32, 33).
Clinically, this was demonstrated in a study
that found that mean 24-hour sputum
volume and QOL were significantly lower
in patients with bronchiectasis after 12
weeks of azithromycin compared with
control subjects (34). These findings are
supported by previous studies (35).
Several studies have evaluated the use
of macrolides as chronic therapy for patients
with NCFB. Two separate meta-analyses
that included seven studies evaluating
various macrolides (five, azithromycin; one,
erythromycin; one, roxithromycin) reported
a decrease in the rates of exacerbation
compared with placebo, as well as
improvements in lung function and QOL
(35, 36). A third meta-analysis that
included studies in children also had
similar findings (37). But there has been
growing concern regarding prolonged
use and potential cardiovascular effects
(i.e., arrhythmias) (38). The three
aforementioned meta-analyses did not
find any increased incidence of
cardiovascular adverse effects, but none
of the trials were powered to detect
these events. Determining the macrolide
regimen with the optimal risk-to-benefit
ratio still requires more studies with
larger sample sizes.
Long-Term Inhaled Antibiotics
Long-term inhaled antibiotics are used for
patients with uncontrolled NCFB, but until
more recently, data on their efficacy have
been lacking. The results from two phase 3,
randomized, control trials (AIR-BX1 and
AIR-BX2) evaluating the usefulness of
inhaled aztreonam lysine for NCFB and that
included 540 patients have been published
(39). Two 4-week courses of inhaled
aztreonam separated by a 4-week off period
did not show significant improvement in
QOL scores compared with placebo, and
adverse events were more common in the
treatment groups. The reasons for these
negative results must be considered closely
before dismissing aztreonam therapy for
NCFB. First, studies have shown that
inhaled aztreonam therapy is effective in
patients with CF, which evaluated a
relatively more homogeneous population
compared with the patients with multiple
etiologies for bronchiectasis studied in the
AIR-BX1 and AIR-BX2 trials. In addition,
dosing was based on previous CF studies,
which may not necessarily be applicable to
NCFB. Second, only about 38% of the
patients were frequent exacerbators
(i.e., more than two exacerbations in the
previous year), suggesting that, because of
the lower severity of the chosen study
population, there was possibly an
underestimation of the effects of aztreonam.
Third, the AIR-BX1 treatment group had a
higher incidence of COPD compared with
placebo, which might have affected the
rate of respiratory adverse events reported.
Last, although Haemophilus influenzae was
excluded, a wide variety of gram-negative
pathogens was included. It is possible that
PULMONARY, SLEEP, AND CRITICAL CARE UPDATE
aztreonam could have been more effective in
patients at risk for worse outcomes
(i.e., those with P. aeruginosa). Future
studies evaluating different dosing regimens,
and in patients with a more severe disease
profile, could help elucidate the role of
inhaled aztreonam in NCFB.
Another randomized placebo-
controlled trial evaluated the efficacy of
inhaled colistin in 114 patients with
bronchiectasis and chronic PA infection
(40). The authors found that the time to
exacerbation was not different between
study groups (165 vs. 111 d; P = 0.11).
The sample size was likely not sufficient to
demonstrate a statistically significant
difference in the primary end point,
although 54 days is a clinically significant
difference. However, in those patients who
had adequate adherence to therapy, there
was a 65-day delay in the median time to
first exacerbation (P . 0.04), reduced
density of PA after 4 weeks (P = 0.001)
and 12 weeks (P = 0.008), as well as
improved QOL scores (P = 0.006) compared
with patients receiving placebo (40).
Adherence continues to play a pivotal role
in chronic antibiotic therapy, and larger
studies are required to clarify the role
of colistin in NCBF with chronic PA
infection.
Brodt and colleagues published a
systematic review of 12 RCTs involving
1,264 patients and a meta-analysis of 8 trials
with 590 patients, finding that inhaled
antibiotics (amikacin, aztreonam,
ciprofloxacin, gentamicin, colistin, and
tobramycin) used for 1–12 months were
more effective than placebo in the
following outcomes: sputum bacterial
load (5 trials), eradicating bacteria from
sputum (6 trials), and reducing the risk
of acute exacerbations (5 trials) (41).
Bronchospasm was reported in 10% of
patients taking inhaled aminoglycosides,
but this side effect was found to be
tolerable (did not influence withdrawal
rates). In summary, there is mounting
evidence that long-term inhaled
antibiotics may have an important role in
the therapy for NCFB. Dose-ranging
studies are still needed to determine the
ideal dosing regimen that balances an
acceptable safety profile with clinically
meaningful positive outcomes.
Surgical Treatment
Surgical treatment has classically been an
option for patients who have localized
Pulmonary, Sleep, and Critical Care Update
bronchiectasis with persistent symptoms
despite maximal therapy, or recurrent
infections with resistant pathogens.
A retrospective review of 109 pediatric
patients who underwent surgical
treatment for NCFB has highlighted
positive outcomes even in patients with
nonlocalized bronchiectasis (42). In this
study, the most common procedure was
segmentectomy (43%) and lobectomy
(38%). Eighty-three children were
monitored for approximately 2 years,
with no procedure-related mortality, and
76% showing improvement in clinical
symptoms. Of note, these surgeons also
performed partial resections of the most
affected areas in patients with diffuse
bronchiectasis, with similar positive long-
term outcomes. Although these results are
promising, studies that have longer
follow-up periods are required before
surgery can be recommended for
nonlocalized bronchiectasis.
Other Therapies
A review by Goyal and Chang compared the
value of combined inhaled corticosteroid
(ICS) and long-acting b2-agonist versus
high-dose ICS monotherapy and found that
the combination inhaler improved subjective
dyspnea and increased cough-free days
compared with high-dose ICS alone (43).
However, a study on the complications
of inhaler use found that there was a
significantly increased risk of hemoptysis
53 days after initiation of ICS/long-acting
b2-agonist or short-acting b2-agonist (44).
Lee and colleagues postulated that
the chronic airway inflammation in
bronchiectatic airways leads to
hypertrophy and tortuosity of bronchial
vessels, making them susceptible to
rupture from the b-adrenergic stimulation
of inhaled b2-agonists (44). More research
is needed, but considering the minor
benefits of inhaled ICS/long-acting
b2-agonist coupled with the possible
increased risk of hemoptysis, caution
should be used when prescribing this
medication to patients with NCFB.
In 2012 a panel of experts conducted an
audit evaluating the adherence of medical
professionals to the British Thoracic
Society’s 2010 NCFB management
guidelines (45). Records from 89
institutions and more than 3,000 patients
were reviewed. The key findings from this
audit were that overall adherence was
variable, with some areas having strong
adherence such in the areas of diagnoses
(z90%), but poor adherence in areas such
as treatment and follow-up (z30%). The
2010 British Thoracic Society guidelines
are only one of two available algorithms
for medical practitioners treating NCFB,
and although adherence is improving
there is still a further need to reinforce
its principles if outcomes are to be
improved.
A study by McCullough and colleagues
highlighted that treatment adherence is
similarly low in patients with NCFB
(40–50%) (46). Furthermore, those who
adhered to treatment, especially with
inhaled antibiotics, had fewer exacerbations
and respiratory symptoms (46). Thus
consistent emphasis on treatment
compliance by physicians is important for
positive outcomes.
Exercise training has been shown to
improve outcomes in COPD, but a study
by Lee and colleagues illustrated that it
can also have beneficial effects in patients
with NCFB. In this study, over a 12-month
period, exercise training reduced the
frequency of exacerbations compared with
control subjects, with a longer time
to first exacerbation if training was
continued for 8 months (47). It is possible
that exercise training may improve both
respiratory muscle conditioning and
mucus clearance.
Future Therapies
After numerous studies illustrated the
positive impact of macrolides in
NCFB, other medications with similar
immunomodulatory properties are starting
to be explored. An RCT by Mandal and
colleagues evaluated the efficacy of a
6-month course of high-dose atorvastatin
on cough production in patients with NCFB
(48). The authors found that it significantly
improved cough scores at 6 months, but
with more side effects in the statin group
(diarrhea/headache). Another ongoing
RCT by Gao and colleagues is seeking to
explore the immunomodulatory benefit of
a novel medication called OM-85, which
has previously shown benefit in patients
with COPD (49). This trial and others
are needed to further validate current
therapies and to evaluate others to help
slow the progression of this debilitating
condition. n
Author disclosures are available with the text
of this article at www.atsjournals.org.
1159
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