PERSPECTIVE HIV and GB Virus C — Can Two Viruses Be Better than One?
activity of intracellular inhibitors of HIV internal- viruses whereby one virus augments the pathoge-
ization. In addition, GBV-C may have cell-specific
effects in certain key cellular targets of HIV, includ-
ing macrophages and dendritic cells. These types
of cells have been shown to be critical in the patho-
genesis of HIV disease and the dissemination of the
virus throughout the infected person. Studies have
demonstrated that variants of GBV-C differ with re-
spect to tissue and cell-type tropism. It is important
to determine whether only specific GBV-C strains
exert a protective effect in HIV-infected persons.
Some combination of the immune-based and direct
antiviral effects described above may come into play
in patients who are dually infected with HIV and
GBV-C.
There is a long history of interactions between
Looking at the Patient — Approaching the Problem of COPD
Stephen I. Rennard, M.D.
Chronic obstructive pulmonary disease (COPD) is
currently the fourth leading cause of death in the
United States and is expected to become the third
leading cause of death by 2020. Cigarette smoking
is the major risk factor, but as many as 20 percent
of patients who have COPD or die from the disease
are lifelong nonsmokers. Despite its importance
as a public health problem, COPD is vastly under-
appreciated. It is underdiagnosed and, when diag-
nosed, commonly undertreated. The need to in-
crease awareness about COPD is a worldwide
problem and has led to a number of initiatives, in-
cluding the Global Initiative for Chronic Obstruc-
tive Lung Diseases (often referred to as GOLD).1
One of the difficulties in understanding COPD
is that it is not a single entity. Rather, it is a collec-
tion of conditions, many of which can be caused by
cigarette smoking as well as by other factors. All
these conditions share a common physiological
abnormality — namely, the limitation of expiratory
airflow. This unifying feature not only helps to de-
fine COPD, but has also helped to direct the devel-
opment and implementation of the currently avail-
able therapies. It is clear, however, from looking at
patients with COPD that this disease is not a simple
problem. Like all complex disorders, COPD affects
far more than a single organ system. Not surpris-
n engl j med 350;10 www.nejm.org march 4, 2004
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nicity of another. Studies have suggested that vari-
ous herpesviruses, including cytomegalovirus and
herpes simplex virus types 1 and 2, may augment
the transmission of HIV and the progression of the
resultant disease. It is highly unusual to find an in-
teraction between viruses that appears to be benefi-
cial to patients who are dually infected. A greater
understanding of the interactions between GBV-C
and HIV may point to therapeutic approaches to
mimicking the clinically protective effects of GBV-C
in patients with HIV infection.
From the Center for Human Virology and Biodefense, Division of
Infectious Diseases and Environmental Medicine, Thomas Jeffer-
son University, Philadelphia.
ingly, the heterogeneous conditions that constitute
COPD can have many diverse extrapulmonary ef-
fects. The famous images of the “pink puffer” and
the “blue bloater,” though not part of our current
clinical paradigms, refuse to disappear, primarily
because they, in an admirably alliterative manner,
describe salient clinical observations (see Figure).
These images, however, only partially reflect the
heterogeneous nature of COPD. Recent studies have
emphasized that patients with similar degrees of
airflow limitation can have obvious and marked
differences in body habitus, exercise performance,
and oxygenation, all of which serves to confuse clin-
ical classification.
The optimal approach to the diagnosis and
management of COPD has remained problematic.
The assessment of airflow is absolutely essential.
Unfortunately, spirometry is rarely used in the rou-
tine assessment of patients with COPD — a failure
that may in part reflect the fact that the forced expi-
ratory volume in one second measures only one as-
pect of the patient’s clinical status. The availability
of easy-to-use, inexpensive equipment that provides
internal quality control to ensure that the measures
meet accepted standards and the introduction of
billing codes permitting routine reimbursement
for spirometry promise to increase greatly the use
965
PERSPECTIVE
Figure. Looking at the Patient with COPD.
COPD may be manifested in striking systemic features. These may vary mark-
edly, even among patients with similar degrees of airflow limitation. The clas-
sic “blue bloater” (left) is characterized by hypoxemia, possibly with carbon
dioxide retention, which may be complicated by pulmonary hypertension and
signs of right-sided heart failure. The “pink puffer” (right), in contrast, is char-
acterized by cachexia, relatively preserved blood gases, and often dyspnea
even when the patient is at rest. Cough and sputum may be prominent in the
blue bloater but may also be present in the pink puffer. Emphysema is often
severe in the pink puffer but may also be present in the blue bloater. Thus, the
two phenotypes illustrated here represent different systemic manifestations
of a complex disease. Many patients with systemic manifestations of COPD
do not resemble either of these patients.
of this crucial test in generalists’ offices. Unfortu-
nately, additional information is still needed to com-
plement the assessment of spirometry. The article
by Celli and colleagues in this issue of the Journal
(pages 1005–1012) helps to address this need.
Improving Online Access to Medical Information
for Low-Income Countries
Barbara Aronson
Over the past two years, the World Health Organi-
zation (WHO) has worked with publishing part-
ners (including the Journal) to improve online ac-
cess to scientific resources as a way of supporting
health professionals, medical researchers, and ac-
ademics in developing countries. WHO helped to
create the Health InterNetwork Access to Research
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Downloaded from www.nejm.org on April 1, 2009 . Copyright © 2004 Massachusetts Medical Society. All rights reserved.
Looking at the Patient — Approaching the Problem of COPD
These investigators developed a multistage scor-
ing system that incorporates a spirometric measure
of airflow together with an assessment of symp-
toms, body habitus, and exercise capacity. Variables
that can be evaluated easily in any office setting were
chosen intentionally, so that the index can be ap-
plied readily and simply. Having established the
measures in a retrospective cohort, the investigators
then prospectively validated the use of their “BODE
index.” (The B stands for body-mass index, O for
the degree of airflow obstruction, D for dyspnea,
and E for exercise capacity.) The acronym, with its
obvious implications, was suggested by Gordon
Snider, a physician-scientist with a career-long in-
terest in COPD, precisely because it provides useful
prognostic information. This index is desperately
needed.
Without doubt, the assessment of airflow is cru-
cial in establishing the diagnosis of COPD and, in
the opinion of many experts, can often help to guide
therapy. The availability of other validated measures,
particularly those that integrate multiple non–air-
flow-related variables, is also essential. Clinicians
will be faced with increasing numbers of patients
with COPD. Fortunately, we will also have increas-
ingly effective forms of therapy. The successful de-
velopment and use of these treatments will require
careful assessment of patients. The BODE index
promises to be an important tool in this regard.
From the University of Nebraska Medical Center, Omaha.
1. GOLD Workshop Report. Global strategy for the diagnosis,
management, and prevention of chronic obstructive pulmonary
disease. Bethesda, Md.: NHLBI, 2003. (Accessed February 12,
2004, at http://www.goldcopd.com.)
Initiative (HINARI, http://www.healthinternetwork.
org), which offers health and medical institutions
in 69 of the world’s lowest-income countries free
online access to a large library of important inter-
national journals. This initiative has been expand-
ed to include an additional 44 countries that qualify
for access to the journals at a very low price. To date,
n engl j med 350;10 www.nejm.org march 4, 2004