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Titre: Adult Bronchiectasis Patients: A First Look at the United States Bronchiectasis Research Registry
Auteur: Timothy R. Aksamit, MD

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Adult Bronchiectasis Patients: A First Look at the United States Bronchiectasis
Research Registry
Timothy R. Aksamit, MD, Anne E. O’Donnell, MD, Alan Barker, MD, Kenneth N.
Olivier, MD, Kevin L. Winthrop, MD, M. Leigh Anne Daniels, MD MPH, Margaret
Johnson, MD, Edward Eden, David Griffith, MD, Michael Knowles, MD, Mark
Metersky, MD, Matthias Salathe, MD, Byron Thomashow, MD, Gregory Tino, MD,
Gerard Turino, MD, Betsy Carretta, MPH, Charles L. Daley, MD
PII:

S0012-3692(16)62354-1

DOI:

10.1016/j.chest.2016.10.055

Reference:

CHEST 810

To appear in:

CHEST

Received Date: 20 August 2016
Revised Date:

3 October 2016

Accepted Date: 28 October 2016

Please cite this article as: Aksamit TR, O’Donnell AE, Barker A, Olivier KN, Winthrop KL, Daniels MLA,
Johnson M, Eden E, Griffith D, Knowles M, Metersky M, Salathe M, Thomashow B, Tino G, Turino
G, Carretta B, Daley CL, for the Bronchiectasis Research Registry Consortium, Adult Bronchiectasis
Patients: A First Look at the United States Bronchiectasis Research Registry, CHEST (2016), doi:
10.1016/j.chest.2016.10.055.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
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Abstract – 249
Text -2498

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Adult Bronchiectasis Patients: A First Look at the United States Bronchiectasis
Research Registry

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Corresponding Author:

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Timothy R. Aksamit, MD, Anne E. O’Donnell, MD, Alan Barker, MD, Kenneth N.
Olivier, MD, Kevin L. Winthrop, MD, M. Leigh Anne Daniels, MD MPH, Margaret
Johnson, MD, Edward Eden, David Griffith, MD, Michael Knowles, MD, Mark
Metersky, MD, Matthias Salathe, MD, Byron Thomashow, MD, Gregory Tino, MD,
Gerard Turino, MD, Betsy Carretta, MPH, and Charles L. Daley, MD for the
Bronchiectasis Research Registry Consortium

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Timothy R. Aksamit, MD
Mayo Clinic
Pulmonary Disease and Critical Care Medicine
200 First St., SW
Rochester, MN 55905
email: aksamit.timothy@mayo.edu

Key words – bronchiectasis, registry, airways, nontuberculous mycobacteria,
Pseudomonas

Short running title – Bronchiectasis research registry

Summary conflict of interests

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TRA has participated in clinical trials sponsored by Bayer, Aradigm, and Insmed but
has not received any personal or research support.
AEO is a PI / received grant support for clinical trials for Aradigm, Bayer, and

AB is a consultant and PI for clinic research study for Bayer

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Insmed and consultant for Bayer, Novartis, and Xellia Pharmaceuticals

KNO’s employer, NIAID, had a Cooperative Research and Development Agreement

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with Insmed, Inc

KLW has received grant support from Insmed and is a consultant for Bayer.

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LAD has no conflicts.
MJ has no conflicts.
EE has no conflicts.

MK has no conflicts.

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DG has received support as a consultant for Aradigm/Grifols

MM participated and received support for clinical trials for Aradigm and Bayer and
consultant for Aradigm/Grifols

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MS has received grant support for clinical trials with Aradigm, Insmed, Gilead,

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Pharmaxis, and JHP Pharmaceuticals and consultant for Insmed.
BT has no conflicts.

GTino has been a consultant for Aradigm /Grifols and Bayer.
GTurino has no conflicts.
BC has no conflicts.
CLD received research support from Insmed

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Funding information – The study was funded by the COPD Foundation and, in part

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(KNO), by the Intramural Research Program of the NHLBI NIH

Abstract

OBJECTIVE: We sought to describe the characteristics of adult bronchiectasis

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patients enrolled in the United States Bronchiectasis Research Registry (BRR).

METHODS: The BRR is a database of non-cystic fibrosis bronchiectasis (NCFB)

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patients enrolled at 13 sites within the United States. Baseline demographic,
spirometric, imaging, microbiologic, and therapeutic data were entered into a
central web-based database. Patients were subsequently analyzed by the presence
NTM.

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RESULTS: We enrolled 1826 patients between 2008 and 2014. Patients were
predominantly female (79%), white (89%), and never smokers (60%) with a mean
age 64±14 years. Sixty-three percent of the patients had a history of NTM disease or

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NTM isolated at baseline evaluation into the BRR. NTM patients were older,

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predominantly female, and had bronchiectasis diagnosed at a later age than those
without NTM. Gastroesophageal reflux (GERD) was more common in those with
NTM whereas asthma, primary immunodeficiency and primary ciliary dyskinesia
were more common in those without NTM. Fifty-one percent of patients had
spirometric evidence of airflow obstruction. NTM patients were more likely to have
diffusely dilated airways and tree-in-bud abnormalities. Pseudomonas and
Staphylococcus aureus isolates were less commonly cultured among patients with

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NTM. Bronchial hygiene measures were used more often in those with NTM;
whereas antibiotics used for exacerbations, rotating oral antibiotics, steroid use, and
inhaled bronchodilators were more commonly used in those without NTM.

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CONCLUSION: Adult bronchiectasis patients enrolled in the US BRR are described

with differences noted in demographic, radiographic, microbiologic, and treatment

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variables based on stratification of the presence of NTM.

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Bronchiectasis is a chronic lung disease characterized by dilatation of airways with
injury to the bronchial walls due to recurrent infection and inflammation. It is

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typically distinguished by whether or not the patient has underlying cystic fibrosis
(CF). Adult non-CF bronchiectasis (NCFB) is heterogeneous and has numerous

causes1-5. Idiopathic bronchiectasis and infection-related bronchiectasis represent

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the majority of adult NCFB in most series4-8. The prevalence of NCFB appears to be
increasing in the United States (U.S.). Seitz and colleagues 9 analyzed a 5% sample of

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Medicare Part B beneficiaries and reported from 2000 to 2007 the prevalence
increased 8.74% annually. In addition, the prevalence of NCFB increases
substantially with aging 10. Furthermore, NCFB imposes a significant financial

$630 million10.

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burden on patients and the U.S. health care system, with annual costs approximating

Despite the significant morbidity of NCFB and significant financial burden,
there are limited data regarding the characteristics of patients with NCFB in the U.S.

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In order to better define the characteristics of NCFB patients and provide a resource

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for clinical trials and other research, the Bronchiectasis Research Registry (BRR)
was established within the COPD Foundation in 2008. The registry includes 13 sites
across the country where patients are enrolled through a centralized database. As
such, the BRR is not a tool to generate population-based prevalence data. This is the
first report describing the U.S. BRR cohort.

Materials and Methods

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The BRR is a centralized database of bronchiectasis patients identified at 13 clinical
sites throughout the U.S. (e-Appendix 1). Adult patients with a physicianestablished diagnosis of bronchiectasis were eligible for inclusion. The Institutional

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Review Board (IRB) of each participating site approved the study as did an

administrative IRB for the data collecting center (DCC) . After providing informed
consent, medical records were queried by a study coordinator or principal

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investigator using standardized recording forms. For purposes of this report, NCFB
is heretofore labelled as bronchiectasis. The exclusion of primary CF patients was

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established based on clinical history, previous sweat chloride results and/or genetic
testing results at the time of enrollment. Exacerbations were recorded based on
historical information. Data were entered through a centralized web-based entry
system at the University of North Carolina. Study coordinators received training

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from the DCC. Quality control (QC) occurred in real-time as the data management

Foundation.

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Spirometry

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system incorporated expected range checks. The BRR is sponsored by the COPD

Spirometry results measured closest to time of enrollment were abstracted from
patient records. Spirometry was considered normal when the FEV1/FVC was ≥ 0.70
and the FVC and FEV1 were >80% of predicted. Airflow obstruction was defined as a
FEV1/FVC < 0.70 and defined as mild, moderate, severe, and very severe
obstruction with a FEV1 of ≥ 80% predicted, ≥50% and <80%, ≥ 30% and < 50%,
and < 30% of predicted, respectively.11 Patients in whom the FEV1/FVC was >0.70

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and the FVC was <80% were labelled as having restriction. A bronchodilator
response was considered present when the FEV1 or FVC improved ≥12% post-

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bronchodilator.

Chest Imaging

Chest computed tomography (CT) scans were read by principal investigators or site

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radiologists.

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Microbiology

A maximum of three respiratory culture results for bacteria, fungi, and
mycobacteria (total maximum of 9 culture results) were abstracted between the 2
years prior to and 90 days after enrollment, defined as the baseline period. We

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recorded positive cultures during the baseline-period, and we subsequently
stratified these results based upon patients’ nontuberculous mycobacteria (NTM)
status. For the purposes of this analysis, we defined “NTM patients” as those with

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either a reported history of pulmonary NTM disease prior to enrollment and/or

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those with one or more NTM isolates in respiratory specimen cultures within the
baseline period.

Treatment

Treatment information was abstracted across several domains, including use of
antibiotics, corticosteroids, bronchodilators, medication for acid suppression,
mucous active agents and measures to enhance bronchial hygiene. Categories of

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antibiotic use included antibiotics for exacerbation only, any suppressive antibiotic,
rotating oral suppressive antibiotics, or inhaled suppressive antibiotics. Measures
to improve bronchial hygiene were defined as any non-pharmacologic measure to

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improve bronchial hygiene.

Statistical Analysis

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The analysis population consists of patients enrolled in the BRR as of July 1, 2014.

Demographic and physical characteristics, medical history, respiratory symptoms,

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imaging findings, spirometry, microbiology culture results and therapies
administered were summarized for all participants with subsequent stratification
based on NTM status as described above. Chi-square tests for categorical data and ttests for continuous data were used to compare patients with NTM to those without

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NTM for the subset of variables for which clinically meaningful relationships were
hypothesized. These comparisons are considered exploratory, and no adjustment

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Results

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for potential confounding variables or multiple comparisons were made.

Demographic and Baseline Characteristics
A total of 1941 patients were enrolled in the BRR as of July 1, 2014. One hundred
and fifteen patients were subsequently excluded from analysis due to withdrawal of
consent (19), diagnosis of NTM without bronchiectasis (11), missing gender (24), or
missing NTM status (61). The evaluable 1826 patients with bronchiectasis enrolled
between 2008 and 2014 were then categorized based on NTM status. Baseline

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information at the time of enrollment is detailed in Table 1. The study population
was predominantly female (79%) and non-Hispanic white (89%). The mean age was
64±14 years with the diagnosis of bronchiectasis in most (77%) patients occurring

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between the ages of 50 and 79. Forty-seven percent had commercial insurance

coverage and 47% had Medicare or Medicaid. Sixty percent were never smokers
and 68% had a prior history of pneumonia. Three percent had primary ciliary

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dyskinesia, 3% pectus excavatum (3%) and 1% HIV infection.

As also shown in table 1, 63% (1158/1826) had co-existent NTM. NTM

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patients compared with non-NTM patients were older, diagnosed with
bronchiectasis at a later age, predominantly female, and had a lower BMI.
Gastroesophageal reflux disease (GERD) was more frequently present in those with
NTM whereas asthma, primary ciliary dyskinesia, and immunodeficiency were more

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common in those without NTM.

Exacerbations were reported at baseline in 64% of patients within the past
two years. Patients with NTM had fewer exacerbations (2.7 + 2.3) during the prior

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two years than those without NTM (3.4 + 3.3. p<0.01) [Table 1].

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Table 2 summarizes respiratory symptoms. The most common symptoms
included cough (73%) that was productive (53%), dyspnea (64%), and fatigue
(50%). Fatigue and hemoptysis were more common in those with NTM whereas
cough was more common in those without NTM. Sweat chloride testing and CF nasal
potential difference measurements were done in 12% and 1.9% of patients, 9% and
11% of which, respectively, were abnormal (data not shown).

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Spirometry
Eighty-five percent of patients had spirometry results reported. No significant
difference was observed between NTM and non-NTM patients (Table 3). Twenty-six

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percent had normal spirometry. Fifty-one percent of patients had obstruction. Three
quarters (76%) of patients with obstruction fell into the mild to moderate category.

Chest Computed Tomography

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patients had a response to aerosol bronchodilator.

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Twenty percent of patients had suggestive restrictive impairment. Only 5% of

CT scans were available for analysis from 1553 (85%) patients. The right middle
lobe (RML) (69%) was the most commonly involved lobe while the upper division of
the left upper lobe (LUL) (44%) the least commonly involved. RML, lingular, right

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upper lobe (RUL), and LUL airway dilation was more common in those with NTM.
(Figure) A single lobe was involved in only 11% of patients and occurred more
commonly in those without NTM. (Table 4) Sixty percent of patients had tree-in-bud

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infiltrates with involvement of all lobes including a higher percentage of tree-in bud-

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infiltrates in NTM patients. Mucoid impaction within the RML, lingula, and RUL was
more common in NTM patients (data not shown). In general, patients with NTM
were more likely to have dilated airways, thickened walls, or mucoid impaction
within the upper lobes, lingula, and middle lobes.

Microbiology

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Of 1826 evaluable patients, 1645 (90%) had at least one type of culture performed
during the baseline period. This included 1314 (72%) patients with at ≥1 AFB
culture, 1406 (77%) with ≥1 bacterial culture, and 1087 (60%) patients with ≥1

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fungal culture performed. For patients with AFB cultures, 484 (37%) isolated M.
avium complex, 130 (10%) isolated M. abscessus/chelonae, and 90 (8%) isolated

other mycobacterial or nocardia species (Table 5). Of those with bacterial cultures

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obtained, 470 (33%) isolated Pseudomonas sp. and 170 (12%) isolated S. aureus. A
variety of other bacterial pathogens were reported. Among those with fungal

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cultures, Aspergillus sp. was most commonly isolated.

While isolation of Pseudomonas species was common among the entire
cohort, it was significantly less common among NTM patients (n=270, 30%) versus

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non-NTM patients (n=200, 40%) [p <0.01]. Similarly, S. aureus was also less
common among NTM patients occurring in 92 (10%) and 78 (15%) of NTM and
non-NTM patients, respectively [p<0.01]. No significant difference in Aspergillus

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isolation was identified between NTM (n=159, 21%) and non-NTM groups (n=52,

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16%) [p=0. 08].

Treatment

Therapies for bronchiectasis were reported in 1826 patients (Table 6). Forty-one
percent (727/1764) of patients had reported antibiotic use for exacerbations only.
Any suppressive antibiotic use was noted in 694 of 1775 (39%) with aerosol
antibiotics reported in 178 of 1759 (10%). As compared to patients without NTM,
patients with NTM had less use of antibiotics for exacerbations only (36% vs. 51%, p

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<0.01) but more use of any suppressive antibiotic (43% vs. 32%, p<0.01). There was
no difference in aerosol antibiotics use. Seven percent of patients (125 of 1771)
used rotating oral antibiotic, and this was less common in those with NTM (6% vs.

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9%, p<0.01).

Inhaled steroids were almost three times more commonly used than oral

steroids (39 % vs. 13%). Inhaled bronchodilators were used in 61% of patients.

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Inhaled and oral steroids were less commonly used in those with NTM compared
with those without NTM (35% vs. 45%, p<0.01, and 10% and 19%, p<0.01,

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respectively) as was use of inhaled bronchodilators (56% vs. 70%, p<0.01).
Medication for acid suppression was used in just over one-third (37%) of patients,
of which 86% were proton pump inhibitors (data not shown). No difference in use
of medication for acid suppression was reported in those with or without NTM.

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Mucous active agents were used in 24% of patients including hypertonic saline in
76% of those using mucous active agents (data not shown). Mucous active agents
were slightly more commonly used in those without NTM.

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Nonpharmacologic measures to improve bronchial hygiene were used in

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56% of patients including 48% (825 of 1719 of patients) using flutter or positive
expiratory pressure (PEP) valve. Chest percussion/postural drainage and high
frequency chest oscillation overall use were similar at 16% and 15%, respectively.
Those with NTM were more likely to use bronchial hygiene, chest percussion, or
flutter or PEP valve compared to those without NTM (59% vs 50% p<0.01; 19% vs.
12% p<0.01, or 52% vs. 40% p<0.01; respectively).

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Discussion
This first report from the BRR describes the largest U.S. cohort of
bronchiectasis patients to date. The Registry has prospectively enrolled over 1900

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NFCB patients, of which 1826 were evaluable. Most are non-Hispanic white women
and lifelong nonsmokers. In this cohort, a large proportion of the patients had a

history of NTM disease or had NTM isolated at their baseline evaluation. Although

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we identified important differences in patients with and without NTM it should be
recognized that this registry was developed as a bronchiectasis registry. As such,

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NTM lung disease specific data domains appropriate for a specific NTM lung disease
registry were not collected. Nonetheless, our findings are in agreement with
published data that most patients with idiopathic bronchiectasis are female
nonsmokers4-8. In addition, we report that those with NTM and bronchiectasis are

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more likely to be female, less likely to have Pseudomonas isolated in sputum, and
older in age at the time of diagnosis than those without NTM.
In agreement with previous studies, we also describe a broad spectrum of co-

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morbidities associated with bronchiectaiss1-3,7,8. Patients with asthma, primary

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immunodeficiency and primary ciliary dyskinesia were less likely to have NTM
whereas those with GERD were more likely to have NTM. Prior investigations have
demonstrated co-existent NTM lung disease and GERD12,13.
In this study over half of the subjects had evidence of airflow obstruction.

Interestingly, a fifth of the patients also had spirometric suggestion of restriction.
Worse lung function in bronchiectasis is associated with more involvement of
bronchiectasis on CT scans , the presence of Pseudomonas species 14-18 and the

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presence of COPD 19. Response to bronchodilator was documented in 5% of
subjects, which is lower than has been reported previously 20.
There appeared to be no difference in spirometry results between those with

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NTM and those without in this cohort of patients, a finding which has not been well
described previously.

This cohort includes descriptive HRCT imaging findings in those with and

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without NTM. Both diseases involve multiple lobes although NTM-associated

bronchiectasis involves an upper lobe and middle lobe distribution more than non-

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NTM bronchiectasis as has been noted by others 21-24.

Treatments for bronchiectasis varied widely within both groups of patients.
Antibiotic use was common and near evenly split between antibiotics used for acute
exacerbations only and suppressive antibiotics. Antibiotics for acute exacerbation

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only were more commonly used for those without NTM, and suppressive antibiotics
were used more frequently in those with NTM. Designation of antibiotics used for
NTM versus bronchiectasis was not specified. A relatively small percentage of

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bronchiectasis patients used aerosol antibiotics, likely reflecting the lack of positive

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clinical trials in this population and the period of time of enrollment. Moreover,
current practice patterns in the participating centers reflect the lack of data to
support rotating oral antibiotics which is similar to recommendations in published
guidelines25.

Even though there is a paucity of data to support its use, bronchodilator
therapy use was noted in over half of bronchiectasis patients and was more
commonly used in those without NTM. Given the central role of mucociliary

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clearance and bronchial hygiene in the management of bronchiectasis it is
surprising that just over half of patients used some measure to improve bronchial
hygiene, the majority of which used a flutter or PEP valve. Consistent use of

by those with NTM compared to those without NTM2,4,25,26.

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bronchial hygiene is in alignment with published literature and was used more often

There are several limitations to our study. Because this study describes a

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cohort of patients enrolled from tertiary referral institutions with interest in NTM

lung disease, the demographic information described is potentially biased including

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over representation of NTM patients. Moreover, the geographical groupings of
participating sites predominated in the Eastern United States. The presence or
absence of co-existent illnesses were based on history. It is difficult to ascertain if
GERD and or co-existent obstructive lung disease was truly present in conjunction

spirometric findings.

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with bronchiectasis or had been ascribed based on compatible symptoms and/or

In conclusion, the BRR has enrolled 1826 evaluable patients with

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bronchiectasis from 13 sites across the United States. Despite baseline

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characteristics of the study population sharing phenotypic similarities this study
notes significant differences in patient groups with or without the presence of NTM.

Acknowledgements:

The BRR is sponsored by the COPD Foundation, a 501 (c) (3) non-profit
organization. The Bronchiectasis Research Consortium would like to acknowledge
the support of the Richard H. Scarborough Bronchiectasis Research Fund, the Anna-

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Maria and Stephen Kellen Foundation, the Bronchiectasis Research Registry
Industry Advisory Committee (Aradigm Corp., Bayer HealthCare Inc., Grifols Inc.,

success of the Registry.

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and Insmed Inc.), and the staff of the COPD Foundation for their commitment to the

It should also be noted that this work would not have been possible without the

coordinators at each of the participating sites.

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comprehensive chart reviews and recording of data by dedicated research

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TRA had full access to all of the data in the study and take responsibility for the
integrity of the data and the accuracy of the data analysis. AEO,
AB, KNO, KLW, LAD, MJ, EE, DG, MK, MM, MS, BT, GTino, GTurino, BC, and CLD
contributed substantially to the study design, data analysis and interpretation and

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Bronchiectasis in Patients with and without Nontuberculous Mycobacteria: A

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First Look at the Bronchiectasis Research Registry

Data
Available
N

No NTM
N = 668

P
value†

1439 (79)

964 (83)

475 (71)

<0.01

64±14

66±12

61±17

<0.01

57±17

59±15

53±19

<0.01

1514 (89)
34 (2)
73 (4)
60 (4)
28 (2)

1003 (91)
7 (1)
41 (4)
41 (4)
16 (1)

511 (85)
27 (4)
32 (5)
19 (3)
12 (2)

<0.01

794 (47)

504 (48)

290 (46)

<0.01

49 (3)
749 (44)
18 (1)
74 (4)

24 (2)
485 (46)
9 (1)
29 (3)

25 (4)
264 (42)
9 (1)
45 (7)

23.2±5.7
19.9, 25.1

22.5±5.5
19.7, 24.3

24.3±5.8
20.3, 26.8

<0.01

1094 (60)
693 (38)
28 (2)

686 (60)
447 (39)
18 (2)

408 (61)
246 (37)
10 (2)

0.74

1657 (96)
56 (3)
18 (1)

1038 (96)
39 (4)
6 (1)

619 (96)
17 (3)
12 (2)

0.02

1823
1456
1709

1684

EP

AC
C

NTM
N = 1158

M
AN
U

1826

TE
D

Gender n (%)
Female
Age, years
Mean±SD
Age at diagnosis, years
Mean±SD
Race/ethnicity, n (%)
Non-Hispanic white
Non-Hispanic black
Hispanic
Asian
Other
Primary insurance, n (%)
Commercial
Medicaid and other state
programs
Medicare
No insurance
Other (including Tricare)
BMI kg/m2
Mean±SD)
q1, q3
Smoking, n (%)
Never
Former
Current
Chest wall deformity, n
(%)
None
Pectus excavatum
Other
Otitis or rhinosinusitis, n

Overall
N = 1826

SC

Table 1. Demographics and clinical characteristics of bronchiectasis patients*

1812

1815

1731

1562

ACCEPTED MANUSCRIPT

222 (23)

166 (29)

<0.01

1745
1778
1783
1789
1775

1187 (68)
350 (20)
515 (29)
841 (47)
142 (8)

758 (69)
217 (19)
298 (26)
577 (51)
87 (8)

429 (67)
133 (20)
217 (33)
264 (40)
55 (8)

0.45
0.60
<0.01
<0.01
0.60

1795
1776
1791
1781

47 (3)
89 (5)
52 (3)

26 (2)
44 (4)
20 (2)

21 (3)
45 (7)
32 (5)

0.25
<0.01
<0.01

1754

70 (4)
1124 (64)

50 (4)
687 (62)

20 (3)
437 (68)

0.14
0.01

992

3.0+2.8

2.7+2.3

3.4+3.3

<0.01

SC

RI
PT

388 (25)

M
AN
U

(%)
Yes
Co-morbidities, n (%)
History of pneumonia
COPD
Asthma
GERD
Rheumatologic disease
Chronic ulcerative colitis or
Crohn’s disease
Primary immunodeficiency
Primary ciliary dyskinesia
Prior tuberculosis, n (%)
Yes
History of pulmonary
exacerbation in the past 2
years, n (%)
Number of pulmonary
exacerbations in the past
2 years, n (%)

AC
C

EP

TE
D

*Percentages and other descriptive statistics calculated after excluding participants with missing
data from the column total. Less than 1% of participants had missing data for all items except the
following: Age at diagnosis (30%), Race/ethnicity (6%), Primary insurance (8%), Chest wall
deformity (5%), History of pneumonia (4%), Otitis or rhinosinusitis (14%), Respiratory distress at
birth (17%), COPD (3%), Asthma (2%), Gastroesophageal reflux disease (GERD) (2%),
Rheumatologic disease (3%), Chronic ulcerative colitis or Crohn’s disease (2%), Primary
immunodeficiency (3%), Primary ciliary dyskinesia (2%), Prior tuberculosis (2%)
†P-values for categorical variables are from chi-square tests, and from T-tests for continuous
variables comparing NTM vs. no NTM patients.

ACCEPTED MANUSCRIPT

Table 2. Symptoms in patients with bronchiectasis by NTM status*
Data
Available Overall
N
(n=1826)
1770
886 (50)

Dyspnea, n (%)
No, not at rest or when
active
Yes, only when active

591
(53)

295
(46)

<0.01

1314
(73)

825
(72)

489
(74)

0.32

951 (53)

568
(50)

383
(59)

<0.01

409 (23)

283
(25)

126
(19)

<0.01

420
(46)
493
(54)

243
(46)
286
(54)

0.98

1804

1788

175

RI
PT

Pvalue†

SC

Daily bouts of coughing, n
(%)
Yes, any
Daily productive cough, n
(%)
Yes, productive cough
Hemoptysis, n (%)
Yes

No NTM
N=668

M
AN
U

Fatigue, n (%)
Yes

NTM
n=1158

1442

663 (46)
779 (54)

AC
C

EP

TE
D

*Percentages and other descriptive statistics calculated after excluding participants with missing
data from the column total. Less than 1% of participants had missing data for all items except the
following: Undue fatigue (3%), Daily bouts of coughing (1%), Daily productive cough (2%),
Hemoptysis (3%), Dyspnea (21%)
†P-values for categorical variables are from chi-square tests and from t-tests for continuous variables
comparing NTM vs. no NTM patients.

ACCEPTED MANUSCRIPT

Table 3. Spirometry test results for patients with bronchiectasis

Mild or Moderate
Obstruction
Severe or Very Severe
Obstruction
Restriction

No NTM
(n=668)

399
(26)

252
(26)

147
(26)

363
(23)

Pvalue‡

SC

1552

229
(23)

134
(24)

790
(51)
555
(36)
235
(15)
317
(20)

502
(51)
366
(37)
136
(14)
200
(20)

208
(51)
189
(33)
99
(17)
117
(21)

47
(5)

33
(5)

14
(4)

0.86
0.11
0.06
0.92

963

TE
D

Post-bronchodilator, n
(%)†
FVC or FEV1 improved
≥12%

NTM
(n=115
8)

M
AN
U

Pre-bronchodilator
findings,
n (%)*
FEV1/FVC≥.70, FVC≥.80 and
FEV1≥.80
(Normal)
FEV1/FVC≥.70, FVC≥.80 and
FEV1<.80
(Near Normal)
Any obstruction

Overall
(n=182
6)

RI
PT

Data
Availabl
e
N

AC
C

EP

*Includes participants with pre-bronchodilator FEV1, FVC, and FEV1/FVC measurements. Any
obstruction is defined as FEV1/FVC<.70. Mild or Moderate Obstruction combines the mild and
moderate groups defined above. Severe or Very Severe Obstruction combines the severe and very
severe groups defined above. Restricted is defined as FEV1/FVC≥.70 and FVC<.80
†Includes only participants with both pre- and post-bronchodilator FEV1 and FVC measurements.
‡P-values for categorical variables are from chi-square tests and from t-tests for continuous variables
comparing NTM vs. no NTM patients.

ACCEPTED MANUSCRIPT

Table 4. Chest computer tomography imaging findings among patents with
bronchiectasis
Data
Availabl
e

N

Overall
(n=1826
)

NTM
(n=1158
)

None indicated†

1553

105 (7)

72 (7)

33 (6)

0.18

Left upper lobe (upper
division)
Lingula

1390

607 (44)
832 (60)

Left lower lobe

1389

830 (60)

Right upper lobe

1392

787 (57)

Right middle lobe

1398

969(69)

Right lower lobe

1388

867 (62)

Only 1 of the above sites

1419

152 (11)

536
(62)
82 (9)

194
(38)
259
(50)
320
(62)
243
(47)
330
(64)
331
(64)
70 (13)

<0.01

1392

413
(47)
573
(65)
510
(58)
544
(62)
639(73)

2-3 of the above sites

1419

479 (34)

>3 of the above sites

1419

683 (48)

276
(31)
464
(52)

203
(39)
219
(42)

1542

610 (40)

1465

366 (25)

295
(52)
87 (16)

1467

528 (36)

1472

556 (38)

Right upper lobe

1474

520 (35)

Right middle lobe

1464

581 (40)

Right lower lobe

1472

611 (42)

134
(24)
168
(31)
123
(22)
162
(30)
185
(34)

<0.01

Left lower lobe

315
(32)
279
(30)
394
(43)
388
(42)
397
(43)
419
(46)
426
(46)

Only 1 of the above sites

1491

119 (8)

78 (8)

41 (7)

<0.01

AC
C

EP

Left upper lobe (upper
division)
Lingula

SC

M
AN
U

TE
D

Tree-in-bud infiltrates n
(%)
None indicated

Pvalue†

RI
PT

Dilated airways, n (%)

No NTM
(n=668)

<0.01
0.13

<0.01
<0.01
0.36
<0.01

<0.01
<0.01

<0.01
<0.01
<0.01
<0.01

ACCEPTED MANUSCRIPT

1491

331 (22)

>3 of the above sites

1491

431 (29)

Any dilated airways,
thickened airway walls, or
mucoid impaction, n (%)
None indicated

1577

40 (3)

26 (3)

14 (2)

0.77

482
(56)
634
(73)
585
(67)
613
(70)
698
(79)
618
(70)
84 (9)

231
(45)
292
(58)
380
(73)
286
(55)
364
(71)
386
(74)
51 (9)

<0.01

280
(30)
537
(58)

211
(39)
267
(49)

713 (52)

1380

926 (67)

Left lower lobe

1399

965 (69)

Right upper lobe

1393

899 (65)

Right middle lobe

1397

Right lower lobe

1396

Only 1 of the above sites

1470

1062
(76)
1004
(72)
135 (9)

2-3 of the above sites

1470

491 (33)

>3 of the above sites

1470

804 (55)

SC

1380

109
(20)
107
(19)

TE
D

M
AN
U

Left upper lobe (upper
division)
Lingula

222
(24)
324
(35)

RI
PT

2-3 of the above sites

<0.01
0.02

<0.01
<0.01
0.12
<0.01

AC
C

EP

*P-values for categorical variables are from chi-square tests and from t-tests for continuous variables
comparing NTM vs. no NTM patients.
†Participant met the inclusion criteria for bronchiectasis but site with dilated airways not identified

ACCEPTED MANUSCRIPT

Table 5. Microbiology results for patients with bronchiectasis
Overall
(n=1826)

NTM
(n=1158)

1406
1406
1406
1406
1406
1406
1406
1406
1406
1406
1406
1406
1406

93 (7)
1037 (74)
116 (8)
49 (3)
170 (12)
470 (33)
76 (5)
35 (2)
20 (1)
15 (1)
13 (1)
30 (2)
5 (0)

68 (8)
669 (74)
72 (8)
26 (3)
92 (10)
270 (30)
54 (6)
24 (3)
9 (1)
9 (1)
5 (1)
25 (3)
3 (0)

25 (5)
368 (73)
44 (9)
23 (5)
78 (15)
200 (40)
22 (4)
11 (2)
11 (2)
6 (1)
8 (2)
5 (1)
2 (0)

0.06
0.57
0.64
0.10
<0.01
<0.01
0.19
0.58
0.10
0.79
0.08
0.03
1.00

1314
1314
1314
1314

319 (24)
657 (50)
484 (37)
130 (10)

302 (33)
653 (71)
484 (52)
130 (14)

17 (4)
4 (1)
0
0

<0.01
<0.01

1314
1314
1314
1314

8 (1)
37 (3)
36 (3)
9 (1)

8 (1)
37 (4)
36 (4)
8 (1)

0
0
0
1 (0)

P-value6

RI
PT

No NTM
(n=668)

SC

M
AN
U

TE
D

Bacterial culture findings , n
(%)
No growth in any culture
Oropharyngeal flora
Haemophilus influenza
Streptococcus pneumoniae
Staphylococcus aureus1
Pseudomonas aeruginosa2
Stenotrophomonas maltophilia
Klebsiella pneumoniae
Moraxella catarrhalis
Achromobacter
Alcaligenes
Serratia marcescens
Burkholderia species
Mycobacterial smear/culture
AFB smear positive
Growth in any culture
Mycobacterium avium complex
Mycobacterium
abscessus/chelonae3
Mycobacterium kansasii
Mycobacterium gordonae
Other mycobacterial species
Nocardia

Data
Available
N

AC
C

EP

Fungal culture findings, n (%)
No growth in any culture
1087
534 (49)
364 (48)
170 (53)
0.10
Aspergillus Sp.4
1087
211 (19)
159 (21)
52 (16)
0.08
Scedosporium apiospermum5
1087
34 (3)
28 (4)
6 (2)
0.18
Other fungal species
1087
392 (36)
284 (37)
108 (34)
0.28
Summary of lower respiratory
culture findings, n (%)
1645
No growth in any culture
136 (8)
85 (8)
51 (9)
Multiple pathogens isolated
1050 (64)
736 (67)
314 (58)
1Includes 30 reported as methicillin sensitive, 58 as methicillin resistant, and 3 coded as ‘MRSA’
from open-ended responses.
2Includes 52 reported as none mucoid, 174 as at least one mucoid, and 17 coded as ‘Pseudomonas’
from open-ended responses.
3Includes 4 reported in open-ended findings that were coded as mycobacterium chelonae and 9
reported as mycobacterium massiliense.
4Includes 56 responses to open-ended findings that were coded as aspergillus not otherwise
speciated.
5Includes 6 responses to open-ended findings that were codes as Scedosporium not otherwise
speciated.
6P-values for categorical variables are from Fisher’s exact tests when counts are less than 10 and
from chi-square tests otherwise comparing NTM vs. no NTM patients..

ACCEPTED MANUSCRIPT

Table 6. Therapies reported for patients with bronchiectasis*

1775
1771

727
(41)
694
(39)
125 (7)

402
(36)
491
(43)
64 (6)

1759

Use of other therapies,
n (%)
On inhaled steroid

1794

On any oral steroid

1789

On inhaled
bronchodilator
On medication for gastric
acid suppression
On mucous active agent

1798

P-value†
NTM vs no
NTM

325
(50)
203
(32)
61 (9)

113
(10)

<0.01

<0.01
<0.01

65 (10)

0.98

696
(39)
237
(13)
1098
(61)
667
(37)
424
(24)

403 (35

293 (45

<0.01

112
(10)
638 (56

<0.01

432
(38)
252
(22)

125
(19)
460
(70)
235
(36)
172
(26)

1730

965
(56)

642
(59)

323
(50)

<0.01

1711

279
(16)

200
(19)

79 (12)

<0.01

1719

825
(48)

568
(52)

257
(40)

<0.01

1716

252
(15)

142
(13)

110
(17)

0.02

1786

TE
D

AC
C

EP

Measures to improve
bronchial hygiene, n
(%)
Uses a measure to
improve bronchial
hygiene
Uses chest
percussion/post
drainage
Uses flutter or positive
expiratory pressure
(PEP) valve
Uses high frequency
chest oscillation

178
(10)

No NTM
(n=668)

RI
PT

1764

NTM
(n=115
8)

M
AN
U

Antibiotic use, n (%)
On antibiotics for acute
exacerbations only
On any suppressive
antibiotic
On rotating oral
suppressive antibiotics
On inhaled suppressive
antibiotics

Overall
(n=182
6)

SC

Data
Availabl
eN

1784

*Percentages and other descriptive statistics calculated after excluding participants with
missing data from the column total. Less than 1% of participants had missing data for all

<0.01
0.43
0.04

ACCEPTED MANUSCRIPT

AC
C

EP

TE
D

M
AN
U

SC

RI
PT

items except the following: On antibiotics for acute exacerbations only (3%), On any
suppressive antibiotic (3%), On rotating oral suppressive antibiotics (3%), On aerosol
suppressive antibiotics (4%), On inhaled steroid (2%), On any oral steroid (2%), On inhaled
bronchodilator (2%), On medication for gastric acid suppression (2%), On mucolytic agent
(2%), Uses a measure to improve bronchial hygiene (5%), Uses chest percussion/post
drainage (6%), Uses flutter or acapella (6%), Uses VEST (6%)
†P-value is from chi-square test comparing NTM vs. no NTM patients..

ACCEPTED MANUSCRIPT

Bronchiectasis in Patients with and without Nontuberculous Mycobacteria: A

69%

62%

60%
%

AC
C

62%

44%
%

EP

57%

Dilated airways-NTM

TE
D

Dilated airways- Overall

M
AN
U

SC

RI
PT

First Look at the Bronchiectasis Research Registry

60%
%

73%
62% %
%

Dilated airways- non NTM

47%

65%
%
58%
%

38%
%

47%
%

50%
64%

64%

FIGURE.
All lobes were involved with the RML (69%) the most and the upper division of the
LUL (44%) the least. Except for the lower lobes, the other lobes were involved to a
greater extent in NTM as compared to non-NTM subjects.

62%

ACCEPTED MANUSCRIPT

Bronchiectasis in Patients with and without Nontuberculous Mycobacteria: A

RI
PT

First Look at the Bronchiectasis Research Registry

Abbreviations: NCFB – non-cystic fibrosis bronchiectasis, NTM – nontuberculous
mycobacteria, BRR – Bronchiectasis Research registry, DCC – data coordinating

SC

center, GERD – gastroesophageal reflux, CF – cystic fibrosis, FEV1 – forced
expiratory volume in 1 second, FVC – forced vital capacity, CT – computed

M
AN
U

tomography, LUL – left upper lobe, RML – right middle lobe, RUL – right upper lobe,
LUL – left upper lobe, RLL – right lower lobe, LL – left lower lobe, AFB – acid fast
bacillus, PEP – positive expiratory pressure, MAC – mycobacterium avium complex,

AC
C

EP

TE
D

BMI body mass index, U.S. – United States, QC – quality control

ACCEPTED MANUSCRIPT

 
e-Appendix 1:
Participating Sites

RI
PT

Mayo Clinic
Pulmonary Disease and Critical Care Medicine
200 First St., SW
Rochester, MN 55905

SC

Mayo Clinic Florida
4500 San Pablo Road
Jacksonville, FL
32224

M
AN
U

Oregon Health and Science University
Pulmonary and Critical Care Medicine UHN
Portland, OR 97239
National Jewish Health
Division of Mycobacterial and Respiratory Infections
1400 Jackson Street, Room J204
Denver, CO80206
University of Texas Health Sciences Center at Tyler
11937 U.S. Hwy. 271
Tyler, TX 75708-3154

TE
D

University of North Carolina at Chapel Hill School of Medicine
7214 Marciso Hall
125 Mason Farm Road
CB #7248Chapel Hill, NC 27599-7248

EP

University of Connecticut Health Center
263 Farmington Avenue
Farmington, CT 06030

AC
C

Cardiopulmonary Branch / NHLBI
National Institutes of Health
10 Center Drive, Room 6-3152
Bethesda, MD 20892
Georgetown University Hospital
3800 Reservoir Road, NW
Washington, DC 20007

University of Miami, Miller School of Medicine
1600 NW 10th Avenue, Room RMSB 7056
Miami, FL 33136
Columbia University Medical Center - NY Presbyterian Hospital
Center for Chest Disease
622 W. 168th Street
New York, NY10032
Online supplements are not copyedited prior to posting and the author(s) take full responsibility for the accuracy of all data.

ACCEPTED MANUSCRIPT

University of Pennsylvania
Pulmonary, Allergy & Critical Care
825 West Gates Building
3400 Spruce Street
Philadelphia, PA
19104
Columbia University
St. Luke’s Roosevelt Hospital, Dept. of Medicine
1000 10th Avenue
New York, NY 10019

TE
D

Barker, Alan, MD
Oregon Health and Science University
3375 SW Terwilliger Blvd
Portland, OR 97239
Email: barkera@ohsu.edu

M
AN
U

Aksamit, Timothy, MD
Mayo Clinic
Pulmonary Disease and Critical Care Medicine
200 First St., SW
Rochester, MN 55905
Center Phone: (507) 284-2511
Email: aksamit.timothy@mayo.edu

SC

Author affiliations:

RI
PT

 

AC
C

EP

Carretta, Betsy, MPH, PMP
Collaborative Studies Coordinating Center: UNC at Chapel Hill
137 E. Franklin Street, Suite 203
Chapel Hill, NC
27514-4145
Center Phone: (919) 962-6971
Email: betsy.carretta@unc.edu
Site Coordinator
Wilkins, Tania*
Senior Biostatistician
UNC Dept. of Biostatistics
Collaborative Studies Coordinating Center
137 E. Franklin St., Ste. 203, CB# 8030
Chapel Hill, NC 27514
Email: wilkinst@email.unc.edu
Daley, Charles L., MD
National Jewish Health
Division of Mycobacterial and Respiratory Infections
1400 Jackson Street, Room J204
Denver, CO80206
Center Phone: (303) 388-4461
Email: DaleyC@NJHealth.org
Online supplements are not copyedited prior to posting and the author(s) take full responsibility for the accuracy of all data.

ACCEPTED MANUSCRIPT

Eden, Edward, MD
St. Luke's - Roosevelt Hospital Center at Columbia University
1000 10th Avenue, Suite 3A-55
New York, NY 10019
Email: EEden@chpnet.org

TE
D

Johnson, Margaret, MD
Mayo Clinic Florida
Davis 7a
4500 San Pablo Rd S
Jacksonville, FL 32224
Email: Johnson.margaret2@mayo.edu

M
AN
U

Griffith, David, MD
University of Texas Health Sciences Center at Tyler
11937 U.S. Hwy. 271
Tyler, TX 75708-3154
Email: David.Griffith@uthct.edu

SC

Daniels, M. Leigh Anne, MD MPH
University of North Carolina at Chapel Hill
Department of Medicine
7213 Marciso Hall
125 Mason Farm Road
CB #7248
Chapel Hill, NC 27599-7248
Email: leighanne_daniels@med.unc.edu

RI
PT

 

EP

Knowles, Michael, MD
University of North Carolina at Chapel Hill School of Medicine
7213 Marciso Hall
125 Mason Farm Road
CB #7248
Chapel Hill, NC 27599-7248
Email: knowles@med.unc.edu

AC
C

Metersky, Mark, MD
University of Connecticut Health Center
263 Farmington Avenue
Farmington, CT 06030-1321
Email: Metersky@nso.uchc.edu

O’Donnell, Anne, MD
Georgetown University Hospital
3800 Reservoir Road, NW
Washington, DC 20007
Email: odonnela@gunet.georgetown.edu
Olivier, Kenneth, MD
National Institute of Allergy and Infectious Diseases (NIAID)
6610 Rockledge Drive, MSC 6612
Bethesda, MD 20892-6612
Email: olivierk@niaid.nih.gov
Online supplements are not copyedited prior to posting and the author(s) take full responsibility for the accuracy of all data.

ACCEPTED MANUSCRIPT

 

M
AN
U

Tino, Greg, MD
Gregory Tino, M.D.
Chief, Department of Medicine
Penn Presbyterian Medical Center
Associate Professor of Medicine
University of Pennsylvania School of Medicine
39th and Market Streets
Suite W-130
Philadelphia, PA 19104
Email: gregory.tino@uphs.upenn.edu

SC

Thomashow, Byron, MD
Columbia University Medical Center - NY Presbyterian Hospital
Center for Chest Disease
622 W. 168th Street
New York, NY10032

RI
PT

Salathe, Matthias, MD
University of Miami, Miller School of Medicine
1600 NW 10th Avenue, Room RMSB 7056
Miami, FL 33136
Email: msalathe@med.miami.edu

TE
D

Turino, Gerard, MD
Columbia University
St. Luke’s Roosevelt Hospital, Dept. of Medicine
1000 10th Avenue
New York, NY 10019
E-mail: gmt1@columbia.edu

AC
C

EP

Winthrop, Kevin, MD MPH
Oregon Health and Science University
3375 SW Terwilliger Blvd
Portland, OR 97239
Email: winthrop@ohsu.edu

162002

Online supplements are not copyedited prior to posting and the author(s) take full responsibility for the accuracy of all data.


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