Respiratory Exchange - Cleveland Clinic · 2013. 12. 20. · 1987 to 2007 and determined that...
Transcript of Respiratory Exchange - Cleveland Clinic · 2013. 12. 20. · 1987 to 2007 and determined that...
RespiratoryExchange
Research and news for
Physicians from the Cleveland
Clinic Respiratory Institute
Winter | 2011
Also in this Issue
Translational Research at Cleveland Clinic's Asthma Center
pg 7
Introducing our Expanded MICU and New Bronchoscopy Suites
pg 6
Pulmonary Sarcoidosis Mouse Model May Aid Discovery of DiseaseMechanisms
pg 10
A Unique Lung Transplant ProgramBy Marie Budev, DO, MPH; Gosta Petterson, MD, PhD; Kenneth McCurry, MD
continued on page 2
One out of every 10 lung transplants in the US was performed
at Cleveland Clinic in 2009. These included three heart/double-
lung and three double-lung/liver transplants. We attribute these
high numbers and good outcomes to more aggressive donor
utilization, teamwork and strong institutional support. We expect
to have performed more than 120 transplants in 2010, based
on our volume estimates through mid-December.
We welcome complex cases, and care for many patients who
have been turned down by other centers for being too old or
having multiple co-morbidities. We evaluate many hundreds of
end-stage lung disease patients every year, from the United
States and elsewhere. The new lung allocation scores (LAS)
have not affected our average wait times, in which almost
one-third of those listed get new lungs in 30 days, and 90
percent are transplanted within a year. Nationally, only 40
percent get a transplant in that time. Although we transplant
more high-acuity cases, our hospital and 30-day mortality
remain low. Our survival rates are generally at or above the
national average.
Cleveland Clinic performed 157 lung transplants in 2009, setting an international record for lungs transplanted
in a single year. The survival outcomes at one year for the patients transplanted in 2009 remains at or above
the national average and our long-term survival also is above the national average.
72580_CCFBCH_ACG.indd 1 1/17/11 12:18 PM
With five lung transplant surgeons and a team of transplant pulmonologists, supported
by specialists in Infectious Disease, Immunology and other specialties, our program
is well-prepared for what may be an annual 200 or more lung transplants in the near
future. Over the years, we have built a professional environment where physicians can
thrive and practice medicine to the best of their abilities. As a result, everyone works
as a team and the patient gets the very best care before, during and well beyond
surgery. We have the support of the full institution, from nurses to administrators.
Our transplant coordinators are experienced, competent and sensitive to our patients.
Kenneth McCurry, MD, was designated as the UNOS primary surgeon and surgical direc-
tor of Heart and Heart-Lung Transplant in 2010. Marie Budev, DO, MPH, was designated
as the UNOS primary physician and medical director in 2009. Gosta Pettersson, MD,
PhD, primary surgeon and surgical director until 2009, continues to study all aspects of
lung transplantation and to refine its techniques.
Cleveland Clinic is a leader in research and innovation in lung transplantation. Team
members lead and participate in multicenter trials, including studies of primary graft
dysfunction, acute rejection therapy, and induction therapy and ex vivo perfusion.
Dr. McCurry has a research appointment in the Department of Pathobiology, where he is
investigating means to increase utilization and developing therapies to improve post-trans-
plant outcomes. His research interests include reperfusion ischemia injury – a persistent
cause of morbidity and mortality in the early post-transplant period. One advantage of high
patient volumes is the opportunity to perform more randomized studies.
Cleveland Clinic recently received two R34 planning grants from the NIH. The first is ex-
amining antibody mediated rejection in lung transplant and its treatment and the second
is looking at lung transplant and chronic rejection.
A Unique Lung Transplant Program continued
Dear Colleagues:I am pleased to present to you the 2011
issue of Respiratory Exchange.
As you will see in the pages that follow,
we have had a busy year at the Cleveland
Clinic Respiratory Institute. Our experts
in Pulmonary, Allergy and Critical Care
Medicine; Thoracic and Cardiovascular
Surgery; Thoracic Imaging; and Pulmonary
Pathology cared for nearly 90,000 patients.
We also saw significant increase in our
staff this past year, with a total of 15 physi-
cians joining our Institute. This growth has
allowed us to expand our existing services
particularly in the areas of lung transplant,
bronchology and medical intensive care as
well as to increase our specialists available
in the community at regional sites.
In this year’s issue, you can read about
our latest clinical programs and research,
including one especially notable highlight,
our lung transplant program performing
157 lung transplants in 2009, a world-record
number for a single center.
Thank you for picking up this issue of
Respiratory Exchange. We hope you enjoy
these articles showcasing our recent work.
For past issues, please visit out website at
http://my.clevelandclinic.org/pulmonary.
Please feel free to contact us at our toll-free
number for physicians, 866.CCF.LUNG
(866.223.5864), if you have any questions or
would like to refer a patient. As always, we
welcome the opportunity to work with you.
Sincerely,
Herbert P. Wiedemann, MD, MBA
Chairman, Cleveland Clinic
Respiratory Institute
2 | Respiratory Exchange
72580_CCFBCH_ACG.indd 2 1/20/11 3:16 PM
Winter 2011 | 3
A greater use of lungs from donation after cardiac death (DCD) could help increase the
number of transplants. Today, most transplanted organs come from donation after brain
death, reflecting a long-standing bias in favor of brain death organs. A 2008 study at
Cleveland Clinic evaluated all DCD lung transplants performed in the United States from
1987 to 2007 and determined that survival after lung transplant using DCD donors was
excellent and, in fact, better than survival after brain-death donation.1
In 2007, Dr. Pettersson performed the world’s first bronchial artery revascularization
(BAR) in lung transplantation. In lung transplant, these arteries are routinely ignored, leav-
ing bronchi dependent on venous blood supply. As a result, serious and sometimes fatal
bronchial healing problems occur in 15 percent of lung transplant patients. Dr. Pettersson
revascularized the bronchi by attaching the patient’s left mammary artery to a major
bronchial artery in the donor lungs. Since then, 26 patients have been transplanted with
BAR at Cleveland Clinic, with 25 patients having excellent airway healing. Assessment of
long-term results (e.g., incidence of BOS) is underway.
A recent study appearing in the Journal of the American Medical Association shows a
wide variability in five-year survival among lung transplant centers in the U.S. It suggests
that the choice of where a patient has lung transplantation may be among the most impor-
tant determinants of success. Although in this study high volume centers (more than 50 a
year) do not always have the best outcomes, at Cleveland Clinic, this is not the case. The
Cleveland Clinic Lung Transplant Program is able to combine high volumes with high
acuity, to achieve outcomes that are at or surpass the national average.
Dr. Pettersson revascularized
the bronchi by attaching
the patient’s left mammary
artery to a major bronchial
artery in the donor lungs.
Since then, 26 patients have
been transplanted with BAR
at Cleveland Clinic, with
25 having excellent air-
way healing. Assessment
of long-term results (e.g.,
incidence of BOS) is
underway. References
1. Mason et al. Should lung transplantation be performed using donation after cardiac death? The United States experience. J Thoracic Cardiovasc Surg 2008; 136:1061-1066.
72580_CCFBCH_ACG.indd 3 1/20/11 3:17 PM
4 | Respiratory Exchange
Antibody-mediated Rejection after Lung Transplant: Is it Clinically Significant?By Carol Farver, MD
The major focus of rejection has been
acute cellular rejection involving specific T
lymphocytes, but the improved detection of
circulating antibodies against the donor lung
present in the lung recipient has introduced
another potential form of graft injury, known
as antibody-mediated rejection (AMR). This
form of rejection is well-documented as a
cause of organ failure in other solid organs,
such as the heart and kidney, but its role in
lung transplantation is not clear. Currently,
a focused effort to study this problem by an
interdisciplinary team of physicians from the
Cleveland Clinic Transplant Center, including
pathologists, pulmonologists, immunologists
and surgeons is underway.
Antibody-mediated rejection is a form of
graft injury thought to be the result of anti-
bodies to donor HLA antigens in the recipient
after transplantation, which cause activa-
tion of complement in the alveoli of the new
donor lung and alveolar injury. This injury
can cause a number of respiratory symp-
toms that may include diffuse pulmonary
infiltrates, severe hypoxemia, blood-tinged
sputum and, in the most fulminant cases, re-
spiratory failure. This clinical picture is quite
nonspecific in this setting and can be difficult
to distinguish from complications of infection
or cellular rejection. It may occur within
minutes or days of transplantation, but also
has been implicated in bouts of unexplained
respiratory illness in these patients up to
two years after surgery.
Lung transplantation is now an accepted and increasingly common therapy for patients with pulmonary disorders
resistant to other therapies and who are progressing toward end-stage lung disease. Though the long-term outcomes
are improving, unfortunately, they remain disappointing compared to those of other solid organs, such as heart and
kidney. The reported median survival is approximately five years and rejection and infection remain the leading
causes of death.
Figure 1. A biopsy from a transplanted lung in a patient with antibody-mediated rejection (AMR). This pathology shows evidence of capillaritis with hemorrhage, hemosiderin-leaden macrophages and acute inflammatory cells within the interstitial capillaries. (Hematoxylin and eosin; 200x).
72580_CCFBCH_ACG.indd 4 1/17/11 12:18 PM
Winter 2011 | 5
The pathologic pattern of injury is simi-
larly nonspecific. The most commonly seen
pathology includes diffuse alveolar damage
(DAD)/acute respiratory distress syndrome
(ARDS) or a small vessel vasculitis (Figure
1), but other patterns of injury also may be
possible. As techniques to measure these
anti-donor antibodies in the peripheral blood
as well as in the transplanted lung have been
developed and improved, it has allowed for
more sensitive detection of them and for
correlation of their presence with both the
clinical symptoms and the lung pathology.
The pulmonary pathology section of the
Pathology and Laboratory Medicine Institute,
including myself and Valeria Arrossi, MD, are
working in conjunction with Marie Budev,
DO, MPH, Medical Director of the Cleveland
Clinic Lung Transplantation Program and
Medhat Askar, MD, PhD, Peter Lalli, PhD,
Diane Pidwell, PhD and Lynne Klingman of
the Allogen Laboratories to study this impor-
tant clinical problem more closely.
Figure 2. A positive immunofluorescence stain for C4d in a lung biopsy from a transplant patient with antibody-mediated rejection. The antibody binds to the capillary within the alveolar wall and produces a linear green immunofluorescent staining pattern, characteristic of C4d activation of the endothelium. (C4d IF; 100x)
We are presently conducting a study that
will measure these antibodies in the blood
before transplantation and at each clinic visit
after transplantation and evaluate positive
staining for antibodies to C3d and C4d as
a measure of complement activation in the
surveillance biopsy specimens taken from the
transplanted lung (Figure 2). We hope this
work will define more clearly the clinical and
pathologic picture of AMR as a first step to
improving outcomes in these patients.
Reach Dr. Carol Farver at 216.225.7695
As techniques to measure
these anti-donor antibodies
in the peripheral blood as
well as in the transplanted
lung have been developed
and improved, it has al-
lowed for more sensitive
detection of them and for
correlation of their pres-
ence with both the clinical
symptoms and the lung
pathology.
72580_CCFBCH_ACG.indd 5 1/20/11 3:18 PM
6 | Respiratory Exchange
Introducing our Expanded MICU and New Bronchoscopy SuitesIncreasing our capacity to better serve you
Cleveland Clinic recently expanded its medical intensive care unit
(MICU) and opened new bronchoscopy suites to meet an increasing
demand for these services.
MICU
Our MICU, led by Jorge A. Guzman, MD, now has 43 beds to better handle higher volumes
due to growth in our lung transplant and critical care transport programs and high-acuity
patients. Board-certified intensivists provide in-house coverage 24/7. We project more than
2,000 admissions per year due to this increased capacity. In view of our high transfer popu-
lation (35 percent of admissions), patient outcomes remain excellent, with mortality rates
below the risk-adjusted predicted values and improving infection rates.
Bronchoscopy Suites
In 2010, we opened four new bronchoscopy suites to accommodate increasing diagnostic
and therapeutic bronchoscopy volumes. We have some of the world’s most extensive experi-
ence with electromagnetic navigation, lung transplant-related airway disease, self-expanding
metallic stents, management of airway complications due to histoplasmosis, benign airway
diseases and metallic stent removal. In 2009, we performed 2,572 bronchoscopies, a 38
percent increase in five years. Importantly, our complication rates remained low.
No Patient Too Sick… No Patient Too Far
Cleveland Clinic’s Critical Care Transport is
designed to help critical care patients any
where in the world get the care they need.
We transport critically ill and injured patients
via ground mobile ICU, rotor wing aircraft
(helicopter), and fixed wing aircraft (jet).
• Our transport teams are staffed with Acute
Care Nurse practitioners (ACNPs), formally
trained as critical care interventionalists
• Treatment can begin during transport, thus
providing the highest possible quality of care
• We can transport patients requiring special
critical care needs including intra-aortic
balloon pumps, ventricular assist devices
or extra corporeal membrane oxygenation
To transfer a patient, call 800.533.5066 The new bronchoscopy suites were possible in part thanks to a generous contribution by Patricia Brundige in memory of her husband, Thomas.
72580_CCFBCH_ACG.indd 6 1/20/11 3:20 PM
Winter 2011 | 7
Research AdvancesCleveland Clinic’s Asthma Center leverages translational research to support and enhance patient care and outcomesBy Sumita Khatri, MD, MS
Physicians and specialists from a variety of medical and surgical disciplines as well
as subspecialties work collaboratively at Cleveland Clinic’s Asthma Center to deliver
state-of-the-art clinical services and novel agents or approaches to diagnose and
treat primary adult and pediatric asthma patients.
Moreover, under the leadership of co-directors
Sumita Khatri, MD, MS, David Lang, MD, and
Serpil Erzurum, MD, the Asthma Center remains
at the forefront of developing innovative treatments
through clinical trials and leveraging translational
research that supports and enhances patient care.
For example, we are involved in a unique research
partnership with the U.S. Environmental Protection
Agency to evaluate whether hospital presentations
for asthma in Northeast Ohio are temporally as-
sociated with poor air quality, and whether certain
sources of air pollution may partially explain pat-
terns of hospital presentations. Our preliminary work
has demonstrated that proximity to major highways
and roadways is a risk factor in asthma morbidity.
Another research project is investigating hyaluronan
(HA) as a central mediator of infl ammation and
remodeling in the asthmatic airway. Our research
will determine the utility of HA as a biomarker for
asthma and disease activity. We also are investi-
gating low molecular weight HA as a therapeutic
for asthmatic infl ammation. Additionally, clinical
investigators are examining the pathways between
HA and lymphocytes that occur within the lung dur-
ing asthmatic infl ammation, which may lead to the
development of new, novel therapeutics.
Cleveland Clinic researchers also are investigat-
ing how angiogenic remodeling is involved in the
genesis of asthma. Circulating CD34+CD133+
pro-angiogenic stem cells are essential in new
blood vessel formation. During their post-natal life,
these cells reside in the bone marrow. Although
rarely found in the peripheral blood circulation,
these stem cells can be rapidly mobilized by
angiogenic factors. These stem cells have opened
new perspectives of angiogenesis and how it may
play a role in the origins of asthma. Our clini-
cal investigators have shown circulating bone
marrow-derived CD34+CD133+ progenitor cells
in asthma are higher than in healthy controls, and
are key players in the initiation of vascular remod-
eling in the airways. More recently, we reported
that these progenitors regulate eosinophil traffi ck-
ing to asthmatic lungs via increased expression of
eotaxin-1, a main chemoattractant for eosinophils.
These progenitor cells release their pre-synthesized
eotaxin content after contact with vascular cells
of allergen-exposed lungs. Circulating progenitors
also have the potential to differentiate into several
lineages relevant to asthma including mast cells
and eosinophils. These fi ndings provide emerg-
ing evidence that circulating pro-angiogenic stem
cells are pro-infl ammatory. Our ongoing research
is investigating whether pro-angiogenic stem
cell-derived eotaxin can serve as a biomarker for
disease outcome, and if inhibition of these stem
cells can benefi t clinical outcomes in asthmatics.
Finally, Cleveland Clinic is collaborating with the
National Institutes of Health in the Severe Asthma
Research Program (SARP), an observational study
to better characterize asthma’s pathology. Through
such NIH-sponsored research programs and
investigator-initiated studies, Asthma Center investi-
gators are making advances in the understanding of
the pathophysiology of asthma, therapeutic targets
for asthma, and epidemiology of asthma. Moreover,
profi ling of asthma enables physicians to better
determine which patients will benefi t from various
therapeutic modalities, such as biologic therapies or
interventions, such as bronchial thermoplasty.
Recommended Reading
Asosingh K, Erzurum SC. Angioplasticity in asthma. Biochem Soc Trans. 2009 Aug;37(Pt 4):805-10.
Asosingh K, Swaidani S, Aronica M, Erzurum SC: Th1- and Th2-dependent endothelial progenitor cell recruitment and angiogenic switch in asthma, J Immunol 2007, 178:6482-6494.
Asosingh K, Hanson JD, Cheng G, Aronica MA, Erzurum SC: Allergen-induced, eotaxin-rich, proangiogenic bone marrow progenitors: a blood-borne cellular envoy for lung eosinophilia, J Allergy Clin Immunol 2010, 125:918-925
Dunnill MS. The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol. 1960 Jan;13:27-33.
Khatri SB, Holguin FC, Ryan PB, Mannino DM, Erzurum SC, and Teague WG. Association of ambient ozone exposure with airway infl ammation and allergy in adults with asthma. J of Asthma 2009; 46: 777-785.
Khatri SB, Newman C, Rose J, Ross K, Pillai M, Holstein A, Tailor S, Hammond S, Norris G. Associations of Air Quality with Asthma During the Cleveland Multiple Air Pollutant Study (CMAPS). Am J Respir Crit Care Med. 2010; 181:A6827.
Norris G, M. Landis M, Gilmour I. EPA Research Highlights: Tracking Air Polution Sources for Exposure,Health, Ecology, and Regulation. EM-Journal of Air & Waste Management Association, 2009.
72580_CCFBCH_ACG.indd 7 1/20/11 3:22 PM
8 | Respiratory Exchange
Bronchial Thermoplasty: A New Asthma Therapy Available at Cleveland Clinic. By Thomas Gildea, MD and Sumita B. Khatri, MD, MS
Bronchial thermoplasty (BT) is a new therapeutic modality recently FDA-approved for the treatment of severe refractory
asthma not well controlled on high-dose inhaled corticosteroids and long-acting bronchodilator therapy. BT involves the
application of radiofrequency energy in a controlled manner to provide thermal treatment to airways. This new procedure,
which occurs in three separate sessions, is now offered as part of the comprehensive management of patients with asthma
in the Respiratory Institute. Clinical trials demonstrate the feasibility, relative safety and improved clinical outcomes in
patients with severe asthma who undergo BT when medical therapies do not control their symptoms. Similar to the criteria
in the multi-center AIR2 clinical trial, patients who are 18 to 65 years old, current non-smokers for the past year, and have
refractory symptomatic asthma on appropriate controller therapy are considered for this treatment at Cleveland Clinic.
Asthma is a chronic inflammatory condition of the airways char-
acterized by episodic symptoms of breathlessness, cough, and
wheezing. The chronic airway inflammation can lead to persistent
airflow obstruction that can be difficult to manage and control, even
with the best available medical therapies. Bronchoconstriction in
asthma is characterized by increased airway smooth muscle (ASM),
airway closure and hyperresponsiveness temporarily reversed with
acute bronchodilators, but medical therapy targeting ASM is not
available. This potential gap in the management of asthmatics is
what is targeted by this new therapeutic modality, BT.
Background on Bronchial Thermoplasty:
The use of this technology to treat airway smooth muscle began with
animal studies which showed feasibility of using radiofrequency ener-
gy to decrease ASM.1 Subsequent clinical studies and trials in patients
that were non-asthmatics or had mild to moderate persistent asthma,
and finally moderate to severe refractory asthma were performed and
helped identify appropriate candidates, anticipated adverse events,
and expected outcomes.2-5
Observational studies in mild to moderate persistent asthmatics
demonstrated a steady improvement in airway hyperresponsiveness
and symptom-free days up to two years after BT. In the Research in
Severe Asthma (RISA) trial, patients with severe asthma undergoing
BT were studied for safety, changes in asthma symptoms and ability to
reduce daily inhaled or oral corticosteroids4. After treatment, there were
reductions in rescue inhaler use and improved asthma quality of life
scores. The Asthma Intervention Research (AIR) trial was a prospective
randomized non-blinded study performed to determine whether asthma
control could be improved after BT. Morning peak flow, rescue medica-
tion use, Asthma Quality of Life Questionnaire (AQLQ) and Asthma
Control Questionnaire (ACQ) scores were all significantly improved.3
With BT treatment, there was an encouraging reduction in the number
of mild exacerbations with 10 fewer mild exacerbations per subject per
year. Cleveland Clinic participated in the latest randomized clinical trial,
the AIR2 trial. This study included a control ‘sham’ group that received
bronchoscopy; however, radiofrequency energy was not delivered across
the BT catheter.5 Results showed a significant improvement in asthma
quality of life in the BT group, a significant decrease in severe exacer-
bations, and an 84 percent reduction in Emergency Department (ED)
visits in those receiving BT.
Clinical trials demonstrate that adverse events can occur with
bronchial thermoplasty, making appropriate patient selection key
to the success of this procedure. The most frequent side effects are
symptoms of airway irritation such as cough, dyspnea, wheeze and
bronchospasm.6 Therefore, close post-procedure monitoring for early
and aggressive management of short-term exacerbations (up to six
weeks after the last session) is warranted. Patients should be aware
that less frequent but severe adverse events can include infections,
pleurisy and bleeding.
What patients can expect:
Once a patient is referred for evaluation for bronchial thermoplasty, our
office will contact the patient, gather outside records, and schedule a
visit with specialists who perform the procedure. Any further necessary
testing will be performed to properly assess candidacy for BT.
A full course of treatment requires three separate bronchoscopic proce-
dures. Each lower lobe is treated in its own procedure and then both
upper lobes are treated in the same procedure. The right middle lobe
is not treated. Each is separated by approximately two to three weeks.
Patients are assessed prior to and on the day of the procedure to ensure
relative disease stability before proceeding with the treatment.5
72580_CCFBCH_ACG.indd 8 1/20/11 3:24 PM
Winter 2010 | 9
Bronchoscopy is performed under conscious sedation, (fentanyl/
midazolam/ topical lidocaine) via a transnasal approach with a flex-
ible bronchoscope. Glycopyrrolate is used to decrease secretions.
Radiofrequency (RF) or thermal energy is directed in the airways by
deploying a wire basket in a catheter via the (2 mm) working channel
with the intent of treating accessible airways 3 to 10 mm in diameter.
Each actuation of the system delivers RF energy to heat the tissue.
The technique requires meticulous catheter placement of each 5 mm
treatment zone with direct approximation, but no overlap. A treatment
map is generated to assure complete, but not duplicate, treatment in
all reachable segments. Patients are observed for airway reactivity,
asthma exacerbations, or other complications during an extended re-
covery and monitoring period during which bronchodilators are given
and spirometry performed. Patients are discharged when they have
clinically recovered and spirometry is within 20 percent of baseline.
To summarize, recent clinical trials demonstrate the feasibility, relative
safety, and improved clinical outcomes in patients with severe asthma
who undergo BT when medical therapies do not control their symp-
toms. Long-term studies are ongoing to evaluate the duration of effect
and safety of BT.
Dr. Thomas Gildea is the Head of the Section of Bronchoscopy in
the Respiratory Institute. He can be contacted at 216.444.6490 or
[email protected]. Dr. Sumita B. Khatri is Co-Director of the Asthma
Center and Medical Director, Bronchial Thermoplasty Program.
She can be contacted at 216.445.1701 or [email protected].
Bronchial Thermoplasty Being Performed at Cleveland Clinic
Differences in airway caliber during bronchoscopy noted between visualized right upper airway (smaller, untreated) and the left lower airway (larger, previ-ously treated) in asthmatic patient.
Catheter deployed making contact and delivering energy (note blanching).
Requirements for Bronchial Thermoplasty at Cleveland Clinic:
• Age 18 – 65 years
• Ongoing severe persistent asthma symptoms despite
treatment with inhaled corticosteroid and LABA therapy:
Corticosteroid dose (beclomethasone equiv.) (μg/day) ≥
1,000, and
LABA dose (salmeterol equiv.) (μg/day) ≥ 100
• Oral corticosteroid dose (mg/day) ≤ 30
• Pre-Bronchodilator FEV1 (% Predicted) ≥ 50%
• Non-smoker for past year with < 10-pack year history
• Absence of other conditions: interstitial lung disease,
Churg-Strauss syndrome, pulmonary hypertension, allergic
bronchopulmonary aspergillosis, arrhythmias, immunosup-
pressant therapy, or need for pacemaker/defibrillator.
For more information or to refer a patient for evaluation, please
contact the thermoplasty coordinator Joan Scharf (scharfj@
ccf.org), Dr. Sumita Khatri ([email protected]) or call the referral
line at 216.445.6266.
References
1. Danek CJ, Lombard CM, Dungworth DL, et al. Reduction in airway hyperresponsiveness to methacholine by the application of RF energy in dogs. J Appl Physiol. Nov 2004;97(5):1946-1953.
2. Miller JD, Cox G, Vincic L, Lombard CM, Loomas BE, Danek CJ. A prospective feasibility study of bronchial thermoplasty in the human airway. Chest. Jun 2005;127(6):1999-2006.
3. Cox G, Thomson NC, Rubin AS, et al. Asthma control during the year after bronchial thermoplasty. N Engl J Med. Mar 29 2007;356(13):1327-1337.
4. Pavord ID, Cox G, Thomson NC, et al. Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma. Am J Respir Crit Care Med. Dec 15 2007;176(12):1185-1191.
5. Castro M, Rubin AS, Laviolette M, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med. Jan 15 2010;181(2):116-124.
6. Cox G, Miller JD, McWilliams A, Fitzgerald JM, Lam S. Bronchial thermoplasty for asthma. Am J Respir Crit Care Med. May 1 2006;173(9):965-969.
72580_CCFBCH_ACG.indd 9 1/20/11 3:24 PM
10 | Respiratory Exchange
Pulmonary Sarcoidosis Mouse Model May Aid Discovery of Disease Mechanisms By Carmen M. Swaisgood, PhD, and Daniel A. Culver, DO
A major limiting factor to discovering the mechanisms involved in
the pathogenesis of sarcoidosis is the lack of an animal model that
approximates the human disease. The models typically used in the past
15 years have been helpful for studying the acute events in Th1- or Th2-
polarized responses to complex protein mixes, such as purified protein
derivative. Progress toward developing an acceptable sarcoidosis animal
model had been hindered by the lack of sarcoid-specific antigens. While
the antigen(s) causing sarcoidosis are not known, increasing molecular
and immunologic evidence point to mycobacterial virulence factors as
strong potential candidates. We recently reported the development of
an antigen-specific sarcoidosis murine model using a microbial peptide
associated with human sarcoidosis granulomas. (Figure 1)
Using a peptide corresponding to a fragment of mycobacterial superoxide dismutase A
(sodA) isolated from sarcoidosis patients, we developed a pulmonary model of sarcoid-
osis granulomatous inflammation. This work was done in collaboration with investigators
from Vanderbilt University, who had previously isolated the sodA peptide and had shown
specific immune responses to it in sarcoidosis patients but not control subjects. Features
of this model strongly resemble the human disease, including:
• Hilar lymphadenopathy and parenchymal infiltrates were present in the sodA-treated
mice, with no gross abnormalities of the heart, liver or spleen and no beads or granulo-
mas found in these tissues.
• Extensive granuloma formation developed throughout the lungs of sodA-treated mice
(Figure 2A). Most noncaseating granulomas were concentric to the bead, had several
multinucleated giant cells and were localized to the bronchoarterial bundle (Figure 2B).
These histological features correlate well with those observed in human sarcoid lungs.
• Macrophages were interspersed throughout the granuloma, albeit most abundantly in
the innermost layers closest to the beads (Figure 3A). In addition, CD4+ T cells were
abundantly present in the middle layers of mouse granulomas (Figure 3B).
• There was a significant increase in lymphocytes in the BAL of sodA-treated compared
to control mice, with a CD4/CD8 skew.
• CD4+ cells from bronchoalveolar lavage responded to the sodA, similar to the immune
responses seen in humans.
Figure 2. Lung Granuloma Formation in Mice Four Days After Challenge. Lungs were paraffin embedded, cut and stained with Hematoxylin and Eosin. (A) Lung of a mouse sensitized and challenged with sodA. (B) A granuloma showing multinucleated giant cell (black arrow) around the bead (b).
(A)
(B)
72580_CCFBCH_ACG.indd 10 1/20/11 3:25 PM
Winter 2010 | 11 Winter 2011 | 11
• Blocking of the Type II major histocompatability complex abolished the immune
recognition of sodA by CD4+ T cells. This correlates with the human disease in which
mycobacterial antigens presented by these MHC Class II alleles are recognized by
sarcoidosis CD4+ T cells.
• As observed in human sarcoid BAL fluid, sodA caused the increase of Th1 cytokines
IL-2 and IFN-γ compared to untreated mice. In contrast, the levels of Th2 cytokines
IL-4 and IL-5 in the untreated and the sodA-treated mice were the same.
This pulmonary sarcoidosis mouse model shows the immunopathological features seen
in active sarcoidosis. These include: a) development of noncaseating granulomas from
peptides unique to sarcoidosis; b) cell type and Th1 cytokine patterns similar to those
observed in sarcoidosis subjects at presentation; c) dependence on MHC Class II alleles
in generating immune responses. This model will facilitate studies aimed at identifying
the relevant mechanisms leading to sarcoidosis resolution or progression to fibrosis.
Contact Dr. Carmen Swaisgood at 216.444.4968 or [email protected] and Dr. Daniel
Culver at 216.444.6508 or [email protected].
Reference
Swaisgood CM, Richter K, Moeller S, Klemenc J, Ruple L, Culver DA, Drake WP. Development of a sarcoidosis murine lung granuloma model using mycobacterial antigen sodA. Am J Respir Cell Mol Biol 2010.
Figure 3. Immunohistochemical Analysis of Leukocytes Present in the Lung Granulomas of sodA-treated Mice. (A) Macrophages (B) CD-4+ T cells
Figure 1. Timeline of Murine Model of Lung Sarcoidosis. Mice were sensitized with an emulsion of Incomplete Freund's Adjuvant (IFA) and sodA peptide on day 1 and challenged via tail vein injection on day 14 with sodA-coupled beads, which embolized to the lungs. Lungs and BAL were collected four days after challenge on day 18.
Day 1 – Sensitization
Day 14 – Challenge
Day 18 – Collect
(A)
(B)
72580_CCFBCH_ACG.indd 11 1/17/11 12:18 PM
12 | Respiratory Exchange
Clinicians for centuries have noted distinct
changes in the breath odor of patients with
certain diseases such as diabetes and renal
failure. However a catalytic point in breath
research was Linus Pauling’s identification
of over 250 breath compounds during the
1970s. Since this time, pivotal advance-
ments in the field of breath testing have
helped revolutionize our understanding of
the components of exhaled breath and their
etiology in disease. With major improvements
in detection technologies (infrared, electro-
chemical, chemiluminescence, of many) and
the application of sensitive mass spectrom-
eters, we are now able to qualitatively and
quantitatively measure the thousands of
identified compounds in exhaled breath.
Providing promise for future technologies,
a growing number of FDA approved devices
have emerged in the past decade for use in
monitoring asthma, diagnosing transplant
organ rejection and H. pylori infection, detect-
ing blood alcohol concentration (BAC), and
for monitoring breath gases during anesthe-
sia, mechanical ventilation, and respiration
among others.
Using highly sensitive equipment such as
selected ion flow tube mass spectrometry
(SIFT-MS) our team at the Cleveland Clinic
has the capability of measuring volatile
organic compounds (VOCs) in the parts per
trillion (ppt) range in human breath. With our
database of hundreds of analyzed samples
and access to multiple diseases our group is
moving towards identifying relevant VOCs in
disease and understanding the origins of VOC
from specific metabolic pathways.
In recent years, one arena we have contrib-
uted extensively to is the understanding of
the breath biomarker, nitric oxide (NO), in
asthma. In the early 1990s NO levels were
found to be elevated in the exhaled breath of
patients with asthma compared to controls
and later linked to eosinophilic airway inflam-
mation. However, initial NO detection devices
were large, cumbersome, and nearly impos-
sible to use outside of the research laboratory.
In 2003 the first NO asthma monitoring
desktop device received FDA clearance
representing a hallmark in new breath test-
ing technology. Advantages of exhaled NO
monitoring in asthma include its non-invasive
nature, ease of repeat measurements, and
use in adult and child populations with severe
airflow obstruction where other techniques
would be difficult or impossible to perform.
Originating from the concept that exhaled breath could serve as a window into the physiological state of the body,
breath analysis has emerged as new frontier in medical testing. Breath testing provides a potential clinical benefit as
a cost effective, non-invasive diagnostic tool for disease of the lung and beyond. With growing evidence of clinical
utility, standardization of methods, and new sensor and detection technologies the stage is set for breath testing
to gain considerable attention and wider application in upcoming years.
Single thin film nitric oxide sensor
Fabricated multiple array of thin film nitric oxide sensors
The Ohio Third Frontier Program at Cleveland Clinic: Advancements in Breath Testing and Sensor DesignBy Raed A. Dweik, MD
72580_CCFBCH_ACG.indd 12 1/20/11 3:26 PM
Winter 2011 | 13
To fully advance the breath analysis fi eld,
there had to be a close collaboration between
technical experts who typically have a device
looking for clinical application, the medi-
cal experts who have the clinical problem
looking for a test/biomarker that can be
helpful in diagnosis or monitoring, and
industry/commercial experts who can build
and commercialize the fi nal product. This
multidisciplinary collaboration is exactly
what we have accomplished in our ongoing
project: “Breath Analysis: Targeted Sensor
Development and Commercialization for
Health Care Diagnostics” that was funded
with a $3.8 million Third Frontier Award
from the Ohio Department of Development
(ODOD). Our team brings together a range
of world-leading capabilities in academia,
industry, and government with extensive
experience in sensor development and clinical
applications including recognized centers of
excellence such as the Electronics Design
Center at Case Western Reserve University
(CWRU), the Center for Industrial Sensors
and Measurement (CISM) at Ohio State
University (OSU), NASA Glenn Research
Center, Makel Engineering, Inc. (MEI),
and the Exhaled Breath Laboratory at the
Cleveland Clinic. Our team is currently devel-
oping several sensors for potential medical
applications including a sensor designed for
a home NO monitoring device for asthma.
The Ohio Third Frontier Program support we
received has resulted in promising prospects
for the future. At OSU a major accomplish-
ment has been successful improvements to
the NO sensor based on the electrochemi-
cal cell design. Based on the evolving OSU
design, NASA Glenn Research Center and
CWRU are currently developing advanced
methods for miniaturization of the NO
sensor technology. This has involved fabrica-
tion of thin fi lm sensors within the NASA
Microsystems Fabrication Clean Room and
testing of the sensor in the Chemical Sensor
Testing Laboratory. Further, the ability to
fabricate multiple, operational single sensors
on the same substrate has been demon-
strated which will allow connecting multiple
miniaturized sensors on a single compact
packaged platform to improve sensitiv-
ity and reduce power consumption. Makel
Engineering has focused on transitioning
the sensors developed by OSU, CWRU, and
NASA into portable systems for early clinical
evaluation at the Cleveland Clinic and later
for home monitoring.
Dr. Dweik, Director of the Pulmonary Vascular
Program, can be reached at 216.445.5763
Recommended Reading
(Dweik RA, contributing author). ATS/ERS Recommendations for Standardized Procedures for the Online and Offl ine Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005. Am J Respir Crit Care Med 171(8):912-930.
Dweik, R. 2005. Nitric Oxide in Exhaled Breath: a Window on Lung Physiology and Pulmonary Disease. In D. S. A. Amann, editor. Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. World Scientifi c, Singapore.
Dweik, R. A., and A. Amann. 2008. Exhaled breath analysis: the new frontier in medical testing. Journal of Breath Researach 2(3):030301.
Dweik, R. A., R. L. Sorkness, S. Wenzel, J. Hammel, D. Curran-Everett, S. A. Comhair, E. Bleecker, W. Busse, W. J. Calhoun, M. Castro, K. F. Chung, E. Israel, N. Jarjour, W. Moore, S. Peters, G. Teague, B. Gaston, and S. C. Erzurum. Use of Exhaled Nitric Oxide Measurement to Identify a Reactive, At-risk Phenotype Among Patients With Asthma. Am J Respir Crit Care Med. 2010 May 15;181(10):1033-41.
Grob, N. M., and R. A. Dweik. 2008. Exhaled nitric oxide in asthma: progress since the introduction of standardized methodology. Journal of Breath Research(3):037002.
Grob, N. M., and R. A. Dweik. 2008. Exhaled Nitric Oxide in Asthma. Chest 133(4):837-839.
Grob, N. M., and R. A. Dweik. 2008. Exhaled nitric oxide in asthma. From diagnosis, to monitoring, to screening: are we there yet? Chest 133(4):837-9.
Pulmonary Hypertension Symposium 2010 Recap
The 7th annual Pulmonary Hypertension Symposium was held
on November 19, 2010 at Cleveland Clinic. The meeting was a
huge success with more than 130 participants who came from 19
states to hear state-of-the-art presentations by 26 distinguished
Cleveland Clinic and visiting faculty.
Summit attendees included physicians and other healthcare
professionals, researchers and scientists, industry representa-
tives, patients and care givers and patient advocacy groups.
Dr. Raed A. Dweik, Chair of the Symposium and Director of the
Pulmonary Vascular Program, presented the inaugural “Award
of Merit” to the key note speaker Dr. Nicholas S. Hill, Professor
of Medicine and Chief of Pulmonary, Allergy and Critical Care
Medicine at Tufts University School of Medicine. This annual
award is presented in recognition of extraordinary contribution
to the basic understanding and/or clinical management
of pulmonary hypertension.
The Ohio Third Frontier Program at Cleveland Clinic: Advancements in Breath Testing and Sensor DesignBy Raed A. Dweik, MD
72580_CCFBCH_ACG.indd 13 1/17/11 12:18 PM
14 | Respiratory Exchange
Developing Breath Biomarkers to Aid Lung Cancer Diagnosis By Peter Mazzone, MD, MPH
Biomarkers are objectively measured indicators of the state of an
individual’s health. They range from commonly measured vital signs to
complex molecular signatures. There has been a tremendous amount
of interest in the development of novel biomarkers for cancer. A cancer
biomarker may help to identify someone at risk of developing cancer,
help to diagnose cancer at an early stage, determine the prognosis from
the cancer, predict or monitor the response to therapy, or advance our
understanding of the pathobiology of the cancer.
Lung cancer biomarkers have improved our management of lung cancer patients. Recent
examples of commonly used lung cancer biomarkers are PET scanning and EGFR muta-
tion analysis. There is promise that the development of novel lung cancer biomarkers
will lead to further improvement in our management of this disease in the near future.
Advances in chemoprevention will be most useful if biomarkers are able to identify those
at greatest risk of developing lung cancer. Advances in surgical and ablative therapies will
be most useful if biomarkers help us to identify lung cancer at the earliest possible stage.
Advances in systemic, targeted and individualized therapies may be developed based on
the discovery of new biomarkers capable of predicting the nature of one’s lung cancer and
the response to specific treatment choices.
A new biomarker can improve on currently used tests by being more accurate, less
invasive, less expensive, and/or novel in its intent. To have a clinical impact, the result of
the test must affect a decision to the benefit of the patient. In addition to being accurate,
an ideal test would be easy to administer, have low risk from its performance and be inex-
pensive. Our lung cancer program has been involved in the study of an unusual source of
biomarkers – the breath.
In prior editions of the Respiratory
Exchange, I have outlined our work in
discovering breath biomarkers for lung
cancer diagnosis. In our most recent work,
(unpublished) we recruited approximately
92 patients with untreated lung cancer and
137 control subjects. The control subjects
were either at risk for developing lung
cancer or presented with indeterminate lung
nodules. Study subjects breathed into a
crude, portable breath collection instrument
that drew tidal mixed expiratory breath over
a colorimetric sensor array. The colorimet-
ric sensors were composed of chemically
Colorimetric sensor array.
Sample of a color fingerprint demonstrating changes in color due to exposure to exhaled breath generated from a colorimetric sensor array.
Recommended Reading
Machado RF, Laskowski D, Deffenderfer O, et al. Detection of lung cancer by sensor array analyses of exhaled breath. Am J Respir Crit Care Med 2005;171:1286-1291.
McCulloch M, Jezierski T, Broffman M, Hubbard A, Turner K, Janecki T. Diagnostic accuracy of canine scent detection in early- and late-stage lung and breast cancers. Int Can Therap 2006;5:30-39.
Mazzone PJ, Hammel J, Dweik RA, Na J, Czich C, Laskowski D, Mekhail T. Lung cancer diagnosis by the analysis of exhaled breath with a colorimetric sensor array. Thorax, 2007;62:565-568. doi: 10.1136/thx.2006.072892.
Mazzone PJ. Analysis of volatile organic compounds in the exhaled breath for lung cancer diagnosis. J Thorac Oncol 2008;3:774-780.
Mazzone PJ. Progress in the development of a diagnostic test for lung cancer through the analysis of breath volatiles. J Breath Res 2008;3:10.1088/1752-7155/2/3/037014.
72580_CCFBCH_ACG.indd 14 1/17/11 12:18 PM
Winter 2011 | 15
reactive dyes printed on a disposable cartridge. The dyes change their color based on the
chemical mixture to which they are exposed. The change in colors is analyzed for patterns
that can discriminate the breath of lung cancer patients. Our initial analysis suggested an
accuracy of around 75 percent for distinguishing lung cancer from controls. The accuracy
improved when we considered subtypes of lung cancer. For example, we were able to
distinguish adenocarcinoma from controls with an accuracy of 80 to 85 percent, and ad-
enocarcinoma from squamous cell carcinoma with an accuracy approaching 90 percent.
The colorimetric sensor array technology used in our most recent work has made exciting
advances since the completion of this project. The latest version of the sensor is com-
posed of pigments printed on a nanoporous medium rather than dyes on a flat surface.
This has led to increased stability of the sensor while maximizing the surface area for
reaction. These changes, in concert with the use of advanced imaging systems, have
improved the sensitivity of the sensor system into at least the low parts per billion level
for all relevant chemical classes (>100-fold improvement over the former system). This
sensitivity is equivalent to that of the canine olfaction system. We have worked with the
sensor developers to design a breath collection interface and delivery system capable of
consistently and comfortably collecting and delivering the alveolar portion of the breath to
the advanced sensor. We will be leading a multi-institutional trial of this system, begin-
ning in Spring 2011. We also will begin to use this system to look at other disease states.
In concert with the colorimetric sensor system, we are studying a second breath analy-
sis technology. Our single photon ionization mass spectrometer is capable of detecting
exhaled volatiles at parts per trillion concentration in real-time. Though this device could
become smaller and easier to use over time, its current utility will be to help identify the
nature of the discriminatory breath components. This information will allow us to refine
the sensor elements of point of care systems, such as the above colorimetric sensor array,
optimizing their accuracy.
In addition to breath analysis, imaging advances are certain to impact the management
of lung cancer. We are currently collaborating with our chest radiology partners to evalu-
ate one of these advances, computer-aided detection of lung nodules applied to chest
X-rays, in a large scale lung cancer screening study supported by the Ohio Department
of Development. Subjects at risk for developing lung cancer are randomized to have the
advanced chest X-ray or a sham chest X-ray. We have recruited approximately 1,300
subjects to date.
The lung cancer screening trial cohort is an ideal group to assist with our breath test
work. In addition, we are hoping to leverage the resources supporting the screening study
to grow our blood biorepository of individuals at risk for developing lung cancer and those
with proven lung cancer. Many lines of blood test development for lung cancer are being
studied. A well-annotated blood biorepository will allow us to participate in blood test de-
velopment and validation studies capable of leading to clinical advances for our patients.
It is an exciting time for lung cancer researchers. Advances in chemoprevention, early
detection, prognostication and prediction of treatment response will all require the de-
velopment of novel lung cancer biomarkers. We are hopeful that we will see progress in
these areas in the very near future.
Dr. Peter Mazzone, Director of the Lung Cancer Program, can be reached at
216.445.4812 or [email protected].
The improved sensor
contains more chemi-
cally reactive elements,
a higher surface area
for interaction with the
breath, and improved
flow across the indica-
tors. The result is a
greatly improved sensitiv-
ity to low concentration
volatiles.
72580_CCFBCH_ACG.indd 15 1/17/11 12:18 PM
16 | Respiratory Institute | Staff Directory 2011
Department of Respiratory, Allergy and Critical Care Medicine
HerbertP.Wiedemann,MD,MBAChairman, Respiratory Institute
216.444.8335
Specialty Interests: critical care (including adult respiratory distress syndrome and sepsis), general pulmonary medicine, exercise testing (dyspnea evaluation)
LoutfiAboussouan,MD
216.839.3820
Specialty Interests: general pulmonary medicine, neuromuscular diseases, sleep medicine, long-term ventilator care
JafarAbunasser,MD
216.444.1997
Specialty Interests: critical care
MuzaffarAhmad,MD
216.444.6506
Specialty Interests: pulmonary function lab, asthma, lung cancer
OlufemiAkindipe,MD
216.444.0569
Specialty Interests: Lung Transplantation
FransiscoAlmeida,MD,MS
216.444.6503
Specialty Interests: Advanced Diagnostic and Interventional Bronchoscopy
RendellAshton,MDAssociate Director, MICU Director, Pulmonary and Critical Care Fellowship Program
216.446.5321
Specialty Interests: critical care, lung cancer, physician education
MarieBudev,DO,MPH
Medical Director, Lung Transplantation
216.444.3194
Specialty Interests: lung transplantation, pulmonary hypertension, gender specific pulmonary issues
RobertCastele,MD
440.878.2500
Specialty Interest: general pulmonary medicine
JeffreyT.Chapman,MD
Director, Interstitial Lung Disease Program
216.444.4222
Specialty Interests: interstitial lung disease, pulmonary hypertension, lung transplantation
ChiragChoudhary,MD
(216) 444-6090
Specialty Interests: critical care
JosephCicenia,MD
216.444.8606
Specialty Interests: advanced diagnostic bronchoscopy, general pulmonary medicine
DanielCulver,DODirector, Sarcoidosis Program
216.444.6508
Specialty Interests: sarcoidosis, interstitial lung disease, hypersensitivity pneumonitis
EhabDaoud,MD
Director, Critical Care Medicine Fellowship Program
216.444.6317
Specialty Interests: critical care
RaedA.Dweik,MD
Director, Pulmonary Vascular Disease Program; Joint Appointment with Pathobiology
216.445.5763
Specialty Interests: asthma, pulmonary hypertension, chronic beryllium disease, critical care, bronchoscopy, nitric oxide in lung physiology and disease, exhaled markers in lung disease
SerpilC.Erzurum,MDChairman, Department of Pathobiology, Lerner Research Institute; Director, Cleveland Clinic General Clinical Research Center; Co-Director Asthma Center
216.445.5764
Specialty Interests: asthma, pulmonary vascular disease, respiratory physiology
SamarFarha,MD
216.444.3229
Specialty Interests: critical care, pulmonary hypertension
AndrewGarrow,MD
216.445.9797
Specialty Interests: critical care medicine, sleep medicine
Respiratory Institute Staff Directory
72580_CCFBCH_ACG.indd 16 1/17/11 12:18 PM
Winter 2011 | 17
ThomasR.Gildea,MD,MSHead, Section of Bronchoscopy
216.444.6490
Specialty Interests: pulmonary hypertension, interventional bronchology, lung transplantation
JorgeGuzman,MD
Head, Section of Critical Care Medicine; Director, MICU
216.445.5765
Specialty Interests: critical care, sepsis, shock
TarikHanane,MD
216.445.5765
Specialty interest: critical care
UmurHatipoglu,MD
Quality Improvement Officer
216.636.5344
Specialty interests: asthma, acute respiratory distress syndrome, general (diagnostic) pulmonary medicine and critical care medicine
GustavoHeresi,MD
216.636.5327
Specialty interests: acute respiratory distress syndrome, pulmonary hypertension, sepsis
DavidHolden,MD
216.986.4000
Specialty Interest: general pulmonary medicine
ManicaIsiguzo,MD
216.839.3820
Specialty Interests: general pulmonary medicine
ConstanceA.Jennings,MD
216.445.4184
Specialty Interests: pulmonary hypertension, pulmonary thrombo-embolism, interstitial lung disease, advanced lung disease
SumitaKhatri,MD,MS
Co-Director, Asthma Center Joint Appointment with Pathobiology
216.445.1691
Specialty Interests: asthma
CharlesLane,MD
216.444.6503
Specialty Interests: lung transplantation, critical care
CatherineLazar,MD
216.445.5444
Specialty Interests: general pulmonary medicine
MichaelMachuzak,MD
Medical Director, Center for Major Airway Diseases
216.444.2718
Specialty Interests: rigid and flex-ible bronchoscopy, endobronchial ultrasound, laser, electrocautery, stent placement, bronchoscopic lung volume reduction, transtracheal oxygen cath-eter placement; lung cancer, pleural diseases, COPD
PeterMazzone,MD,MPH
Director, Lung Cancer Program
216.445.4812
Specialty Interests: lung cancer, critical care, physician education
GlennMeden,MD
Chief, Division of Pulmonary and Critical Care Medicine at Hillcrest Hospital, Director, ICU at Hillcrest Hospital
440.312.7140
Specialty Interests: general pulmonary, critical care
AtulC.Mehta,MDChief Medical Officer, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
216.444.2911
Specialty Interests: lung transplantation, lung volume reduction surgery, endobron-chial and bronchoscopic procedures and interventions, transtracheal oxygen therapy
OmarA.Minai,MD
216.444-6500
Specialty Interests: pulmonary hypertension, interstitial lung diseases, lung cancer, COPD, sleep apnea
KathrinNicolacakis,MD
216.444.6500
Specialty Interests: general pulmonary medicine
ThomasOlbrych,MD
440.312.7140
Specialty Interests: general pulmonary medicine, cystic fibrosis, lung transplantation
MitchellOlman,MDJoint Appointment with Pathobiology
216.445.6025
Specialty interest: interstitial lung disease
BeverlyV.O’Neill,MD
Vice President, Medical Operations Euclid Hospital
216.692.7848
Specialty Interests: general pulmonary medicine, long-term ventilator patients
JosephG.Parambil,MD
216.444.7567
Specialty Interests: interstitial lung disease, pulmonary hypertension, general pulmonary medicine
72580_CCFBCH_ACG.indd 17 1/17/11 12:19 PM
18 | Respiratory Institute | Staff Directory 2011
BohdanPichurko,MDDirector, Pulmonary Function Lab
216.445.6789
Specialty Interests: general pulmonary medicine
JenniferRamsey,MD,MS
216.445.8407
Specialty Interests: critical care and general pulmonary medicine
DeborahRathz,MD,PhD
Joint Appointment with Emergency Medicine
216.445.8318
Specialty Interests: critical care
AnitaReddy,MD
216.444.4506
Specialty Interests: critical care, acute lung injury, interstitial lung disease, lung transplant
MadhuSasidhar,MD
Head, Section of Respiratory Therapy
216.445.1838
Specialty Interests: critical care, lung cancer, general pulmonary medicine
JamesK.Stoller,MD,MS
Executive Director, Leadership Development; Chairman, Education Institute
216.444.1960
Specialty Interests: clinical epidemiology, alpha1-antitrypsin deficiency, respiratory therapy
CarmenM.Swaisgood,PhD
Joint Appointment with Pathobiology
216.445.6153
Specialty Interests: sarcoidosis, interstitial lung disease, asthma
AdrianoTonelli,MD
216.444.0812
Specialty Interests: pulmonary hypertension
Section of Allergy and Clinical Immunology
DavidM.Lang,MDHead, Section of Allergy and Clinical Immunology; Director, Fellowship Program
216.445.5810
Specialty Interests: asthma, allergic disorders, sinusitis, urticaria, anaphylaxis, latex allergy, aspirin sensitivity
SusanAbouhassan,MD
216.444.9536
Specialty Interests: general allergy and clinical immunology
MarkA.Aronica,MD
Joint Appointment with Pathobiology
216.444.6933
Specialty Interests: asthma, allergic disorders
SandraHong,MD
440.204.7400
Specialty Interests: allergy, asthma
FredH.Hsieh,MD
Joint Appointment with Pathobiology
216.444.3504
Specialty Interests: asthma, allergic disorders, mast cell function
RachelKoelsch,MD
216.444.6933
Specialty Interests: pediatric and adult allergic rhinitis, asthma, food allergies, bee and wasp sting allergy, eczema, medication allergies, hives
LilyC.Pien,MD
216.444.6933
Specialty Interests: allergic rhinitis, asthma, drug allergies, latex allergy, medical education
CristineRadojicic,MD
216.444.6933
Specialty Interests: pediatric and adult allergic rhinitis, asthma
PARTneRS In oTheR DePARTMenTSDiagnostic Radiology
Section of Thoracic Imaging
MoulayMeziane,MDHead, Section of Thoracic Imaging
216.444.0282
Specialty Interests: thoracic radiology, CT, transthoracic chest biopsies, oc-cupational lung diseases, lung cancer
AhmedEl-Sherief,MD
216.445.7050
Specialty Interests: thoracic imaging
RuffinJ.Graham,MD
216.444.8756
Specialty Interests: pulmonary thromboembolism, lung cancer and thromboembolic disease
OmarLababede,MD
216.444.9014
Specialty Interest: thoracic imaging
72580_CCFBCH_ACG.indd 18 1/17/11 12:19 PM
Winter 2011 | 19
CharlesLau,MD
216.444.1014
Specialty Interest: thoracic imaging
Tan-LucienH.Mohammed,MD
216.444.3867
Specialty Interests: cardiopulmonary imaging/transplantation imaging, interstitial lung disease, upper airway disease
RahulRenapurkar,MD
216.445.7050
Specialty Interest: thoracic imaging
BarbaraRisius,MD
216.444.6422
Specialty Interest: thoracic radiology
RuchiYadav.MD
216.445.7050
Specialty Interest: thoracic imaging
Pulmonary Pathology
CarolF.Farver,MD
Director, Pulmonary Pathology
216.445.7695
Specialty Interest: pulmonary pathology
AndreaArrossi,MD
216.444.9120
Specialty Interests: pathology of interstitial lung disease, and pleural and pulmonary tumors
CharlesV.Biscotti,MD
216.444.0046
Specialty Interests: cytopathology, gynecologic pathology
Thoracic and Cardiovascular Surgery
GöstaPettersson,MD,PhDVice Chairman, Thoracic and Cardiovascular Surgery
216.444.2035
Specialty Interests: lung and heart-lung transplantation
DouglasJohnston,MD
216.444.5613
Specialty Interests: lung and heart transplantation
GonzaloGonzalez-Stawinski,MD
216.444.6708
Specialty Interests: heart transplantation, lung transplantation, transplant immunology, reoperative adult cardiac surgery
KennethMcCurry,MD
Surgical Director, Lung Transplantation Joint Appointment with Pathobiology
216.445.9303
Specialty interests: lung and heart transplantation, ventricular assist devices, heart failure surgery, and lung and heart ischemia- reperfusion injury
NicholasG.Smedira,MD
Surgical Director, Kaufman Center for Heart Failure
216.445.7052
Specialty Interests: lung and heart-lung transplantation; pulmonary thromboendarterectomy
Section of General Thoracic Surgery
ThomasW.Rice,MDHead, Section of General Thoracic Surgery
216.444.1921
Specialty Interests: esophageal, pulmonary, mediastinal, chest wall and diaphragm surgery; minimally invasive (laparoscopic and thoracoscopic) and pediatric general thoracic surgery; lung volume reduction surgery
DavidMason,MD
216.444.4053
Specialty Interests: general thoracic surgery, lung transplantation, minimally invasive thoracoscopic and laparaoscopic surgery, lung cancer, esophageal cancer, malignant mesothelioma
SudishMurthy,MD,PhD
Surgical Director, Center for Major Airway Diseases
216.444.5640
Specialty Interests: esophageal, pulmonary, mediastinal, chest wall and diaphragm surgery; minimally invasive lung volume reduction surgery; lung transplant surgery
Respiratory Exchange
Herbert P. Wiedemann, MD, Medical Editor
Megan Frankel, Marketing Manager
Ann Milanowski, Managing Editor
Michael Viars, Art Director/Designer
Respiratory Exchange is written for physi-cians and should be relied upon for medical education purposes only. It does not provide a complete overview of the topics covered and should not replace the independent judgment of a physician about the appropriateness or risks of a procedure for a given patient.
© 2011 The Cleveland Clinic Foundation
Stay Connected to Cleveland Clinic
72580_CCFBCH_ACG.indd 19 1/17/11 12:19 PM
The Cleveland Clinic FoundationRespiratory Institute / AC311 9500 Euclid Avenue Cleveland, OH 44195
10-PUL-002
R e s p i R at o R y e x c h a n g e R e s e a R c h a n d n e w s f o R P h y s i c i a n s f R o m
t h e c l e v e l a n d c l i n i c R e s P i R a t o R y i n s t i t u t e
c o n t a c t u s
General Patient Referral 24/7 hospital transfers or physician consults
800.553.5056
Pulmonary Appointments/Referrals 216.444.6503 or 800.223.2273, ext. 46503
Allergy Appointments/Referrals216.444.3386 or 800.223.2273, ext. 43386
On the Web at clevelandclinic.org/pulmonary
s e R v i c e s f o R P h y s i c i a n s
Physician Directory
View all Cleveland Clinic staff online at clevelandclinic.org/staff.
Track Your Patient’s Care Online
Whether you are referring from near or far, DrConnect offers secure
access to your patient’s treatment progress at Cleveland Clinic. To
establish a DrConnect account, visit clevelandclinic.org/drconnect
or email [email protected].
Remote Consults
Request a remote medical second opinion from Cleveland Clinic.
MyConsult is particularly valuable for patients who wish to avoid the
time and expense of travel. Visit clevelandclinic.org/myconsult, email
[email protected] or call 800.223.2273, ext 43223.
Cert no. SW-COC-001530
Save the Date!June 16-19, 2012
17th World Congress for Bronchology, and the
17th World Congress for Bronchoesophagology
Cleveland, Ohio
s e R v i c e s f o R Pa t i e n t s
Medical Concierge
Complimentary assistance for out-of-state patients and families
800.223.2273, ext. 55580, or email [email protected]
Global Patient Services
Complimentary assistance for national and international
patients and families
001.216.444.8184 or visit clevelandclinic.org/ic
72580_CCFBCH_ACG.indd 20 1/20/11 3:28 PM