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The satellite meeting
“Dyspnea: Mechanisms and Management” was held at the Joan Kroc Peace and
Justice Center at University of San Diego the two days prior to the main
IUPS meeting. The meeting was held not only to address the latest research
investigating dyspnea, but also to discuss the prevailing problems for
research in this field and the problems faced by patients who suffer this
debilitating symptom. The beautiful campus setting at USD gave us a
panoramic view of San Diego and the staff there did everything needed to
make the meeting run smoothly.
“Shortness of breath” or “Dyspnea” is a prominent symptom of serious
diseases of the lungs and heart. Dyspnea is a powerful, very uncomfortable,
and sometimes frightening sensation. Many people with chronic lung or heart
disease become “respiratory cripples” because they alter their lives to
avoid experiencing dyspnea, others cannot even escape dyspnea at rest, one
of the worst problems for many people in the last weeks of their lives.
Chronic lung and heart diseases are increasing in our society and half of
the patients admitted to major hospitals report dyspnea—–that’s equal to the
number reporting pain. Dyspnea is reported by about 25% of the general
public over 40 years old making it one of the most common symptoms that
cause people to seek medical care. The presence of dyspnea predicts
mortality with a relative risk of 2, equal to chest pain. Failure to
adequately perceive dyspnea has been implicated in the risk of asthma death.
Despite the strong association of dyspnea with distress and mortality,
understanding of the neurophysiology of dyspnea has lagged far behind the
understanding of pain, with a consequent lag in treatment options. To
stimulate interdisciplinary thinking and collaboration about dyspnea we
brought physiologists together with nurses, physicians, therapists, and
patients, many of whom had not met together before. We had nearly 60
attendees, with a wide range of scientific backgrounds and countries
represented.
The symposium covered physiology, psychology, and clinical issues in four
speaker sessions and three discussion workshops. In addition to invited
speakers we enjoyed both short talks and posters of volunteer presentations
as well as an historical after-dinner talk by one of the pioneers in the
field, Abe Guz (Charing Cross Hospital, UK). Guz pointed out that this was
the first two-day symposium focused entirely on dyspnea since 1965, and that
he was delighted to have attended both (along with John Severinghaus). We
shared all meals during the symposium, and the evening reception and dinner
on the first day ensured that our meeting was in accord with the etymology
of the word “symposium.”
The symposium was opened by lead organizer Andrew Binks (Harvard School of
Public Health, USA), who explained that the first three speaker sessions
were organized to cover the distinct physiological mechanisms underlying the
three currently identified distinct sensations of dyspnea: the perception of
the urge to breathe (air hunger), the perception of increased work/effort of
breathing, and the perception of asthmatic tightness; the fourth speaker
session and two of the workshops were devoted to clinical issues.
In the session on physiology of air hunger, the first speaker, Bob Banzett
(Harvard School of
Public Health, USA) made several key points: first, that although air hunger
is only one of several sensations that can contribute to dyspnea, it is
perhaps the most unpleasant and frightening one. He then discussed the
probable neural origin of air hunger in a corollary copy of respiratory
center motor activity projecting to the cerebral cortex. He presented
several lines of evidence showing that air hunger is distinct from
work/effort—including data showing that ratings of work/effort are greatly
increased during voluntary hyperpnea under partial neuromuscular block,
while air hunger remains at zero. Finally he discussed the profound
reduction of air hunger produced by tidal volume stimulation of pulmonary
stretch receptors. Takashi Nishino (Chiba University, Japan) then spoke
about the effect on dyspnea of inhaled aerosol furosemide, which stimulates
slowly adapting pulmonary stretch receptors. He presented evidence that
furosemide reduces air hunger during breath hold in humans, and reduces
behavioral escape responses during airway occlusion in lightly anesthetized
cats. He went on to show exciting evidence of beneficial effects on
intractable dyspnea in selected clinical cases. In addition to further
informing us about the neural mechanism of air hunger relief, his
presentation offered a possibility for an animal behavioral model of dyspnea,
which we currently lack. Julie Wenninger took up the theme of animal models
in her subsequent volunteer presentation on ablation of the Pre-Boetzinger
complex in goats..
The second session was intended to cover the mechanisms of sensations of
work and effort to breathe. Paul Davenport (University of Florida, USA)
pointed out that obstruction of the airways and the consequent increased
mechanical work of breathing is one common cause of respiratory discomfort,
but that ordinarily the load faced by the respiratory muscles is not
consciously perceived. He hypothesized that the transition from unconscious
to conscious perception of breathing is gated, and provided evidence using
measurement of evoked potentials during external respiratory loads. He
described a model for neural gating of afferent information from the lungs
and respiratory muscles. Simon Gandevia (University of New South Wales,
Australia) spoke of the role of motor command, and the possibility that the
disparity of mechanoreceptor feedback and motor command gives rise to
breathlessness. He also discussed the potential of C-fiber afferents
innervating the pulmonary parenchyma to give rise to respiratory
sensations—-further investigation in this important area could lead to
identification of a distinct, fourth form of dyspnea.
The third session on mechanism covered a more controversial area, the
sensations of asthma and their mechanisms. Two leaders in this field shared
different views on the origins of sensations experienced during an asthma
attack. Richard Schwartzstein (Harvard Medical School, USA) described the
sensations involved with asthma and how he uses questionnaires to overcome
patient’s communication problems in accurately describing the sensations
they experience during an asthma attack. “Tightness” is prevalent sensation
in asthma and is unique to asthma. Schwartzstein spoke about the possible
relationship between tightness and hyperinflation during bronchoconstriction.
He pointed out the different interpretations that may arise depending on
whether investigators ask patients or subjects to focus on “tightness” or on
more general terms such as breathing discomfort or breathing difficulty.
Schwartzstein presented evidence from both clinic and lab showing that
“tightness” can occur in the absence of hyperinflation. He went on to give
evidence that the sensation of “tightness” is derived from intrapulmonary
receptors, rather than from respiratory muscles afferents. Denis O’Donnell
(Queen’s University, Canada) described a role for lung hyperinflation and
modified respiratory muscle activity in generating discomfort in asthmatics.
He discussed the increased load on inspiratory muscles at high lung volumes,
and their reduced effectiveness at shorter working length. He showed
evidence that the increase in lung volume (or more specifically, the
resultant decrease in inspiratory capacity) is the best predictor for
increases in dyspnea in obstructive disease. More specifically, O’Donnell
showed “tightness” increases with worsening hyperinflation, and that
tightness can occur with hyperinflation in the absence of
bronchoconstriction. He posited that the sensation arises from neuromechanical
dissociation, or the discrepancy between motor command and resultant
afferent feedback. Clearly, these apparently conflicting views need to be
resolved with data obtained in mutually agreeable experiments.
Recent advances in the understanding of the central mechanisms of dyspnea
have been made using functional brain imaging techniques (fMRI and PET).
However, brain imaging studies pose challenges for those investigating
respiratory physiology and psychophysics. Changes in blood oxygen and carbon
dioxide are common interventions for the respiratory physiologist, but these
changes also cause fluctuations in cerebral blood flow unrelated to neural
activity; therefore, they have the potential to produced artifacts. Karl
Evans (Harvard Medical School, USA) is a psychiatrist and physiologist who
is fully aware of these problems after addressing them in several studies
investigating neural correlates of dyspnea. Evans explained some fundamental
principles, problems and solutions of brain imaging and then described some
of the recent findings. The data revealed neural activations associated with
air hunger in the cingulate cortex, amygdala, thalamus and hypothalamus,
evolutionarily old areas of the cortex important in behavioral responses.
Evans went on to relate these activations to similar activations caused by
pain and by anxiety.
Lewis Adams (Griffith University, Australia) led a workshop on measurement
of dyspnea, and covered a wide range of issues relating to measurement of
clinical dyspnea, laboratory dyspnea, how to compare the two, and what
measures might best assess the outcome of treatments. The first important
theme to emerge was the desirability of measuring dyspnea by the report of
the patient or subject, rather than inferring dyspnea from functional
outcomes such as FEV1 or six-minute walk distance (as one discussant put it,
a defining moment in pain care was the acceptance of the concept that “pain
is what the patient says it is”). From this arose a conversation regarding
how to better measure what the patient or subject feels, including the need
to measure the several distinct sensations covered in the first portion of
the symposium, and in addition, the relatively unexplored concept that
quasi-independent dimensions of sensory intensity and aversive emotional
response of dyspnea should be measured. Bob Lansing (University of Arizona,
USA) led discussion on developing behavioral measures that could be used to
measure the aversiveness of dyspnea in both humans and animals, such as
those that have been used in the fields of pain, thirst, and hunger. It was
clear from the comments during this session that we need to be cognizant of
the difference between clinical dyspnea and laboratory dyspnea, but there
was also hope expressed that, by continuing to interact in meetings such as
this one, clinical and laboratory scientists would create and use measures
that better translate findings between the lab and clinic.
A problem faced by pulmonary physicians is the treatment of patients who
report dyspnea without any apparent underlying disease or condition to
explain the symptom, i.e., “idiopathic dyspnea,” the topic of the second
workshop. Schwartzstein opened this session with a description of the gray
area between physiological and psychological origin of dyspnea, pointing out
that although presence of any lung disease usually rules out the label
idiopathic dyspnea, many pulmonary patients seems to suffer dyspnea
disproportionate to their physiological deficit. The discussion considered
the possible distinctions and similarities among idiopathic dyspnea,
hyperventilation syndrome, and panic disorder. Several participating
clinicians reported that patients with idiopathic dyspnea commonly describe
it as “unable to get satisfying breaths.” Although it seems likely that
purely “neurogenic” dyspnea exists, discussants pointed out that there is a
lack of data on how much dyspnea someone should feel for a given deficit in
lung function, and that many patients probably experience disproportionate
dyspnea. The patients in the audience described the role of situation or
environment in modulating their dyspnea; how the sense of lost control in
some situations may induce a sense of panic that exacerbates dyspnea.
Several participants discussed evidence that pulmonary rehabilitation can
desensitize a patient to dyspnea such that the same intensity of reported
dyspnea causes less anxiety or panic. The patient advocates reported
enthusiasm of COPD patients for rehabilitation programs, and the difficulty
of obtaining health insurance coverage for them.
The latter part of the second day was mainly occupied with clinical issues,
and how they related to the foregoing physiology. Jessica Corner
(Southampton University, UK), an expert in palliative care, began the
session on “Quality of Life and Palliative Care” by emphasizing the need for
a broader approach to symptom management that includes non-pharmacological
intervention. She described the efforts of her group and others to explore
other therapeutic strategies particularly those that recognize the
emotional, social and financial impact of severe breathlessness that occurs
in late stage disease: family disruption, isolation, loss of employment,
depression, and anxiety. Corner reviewed recent research that demonstrates
the value of integrated interventions including psychotherapy, pulmonary
rehabilitation, and nurse management techniques. She reported success in
establishing a dyspnea management protocol as recognized standard of care in
the UK. Research is needed to independently evaluate the efficacy and
mechanisms of these and other forms of intervention and developing models
for combining them with pharmacological interventions over the escalating
course of disease. Paula Meek (University of New Mexico, USA) presented
arguments in favor of different dyspnea measures for assessing the treatment
of dyspnea and its clinical impact. She outlined some of the difficulties in
combining and relating measures of immediate perception, common in
laboratory studies using visual analog or Borg scales, and the secondary
effects commonly measured by life-impact scales. For example, as impairment
worsens over time a patient may maintain a low level of dyspnea, but at the
expense of progressively reducing their daily activities. In future studies
there is a need to develop measures of the emotional or distressing
dimensions of dyspnea particularly as they relates to symptom severity and
the motivation to seek care.
John Hansen-Flaschen (University of Pennsylvania, USA) led the final
workshop on dyspnea in critical care and palliative care. One of the key
themes of this workshop was using the patient’s level of comfort as an
outcome criterion for adjusting mechanical ventilation. It was posited that
“patient-centered ventilation” might reduce required sedation. Although some
expressed doubts about the ability of such patients to communicate what they
feel, several clinicians in the group reported success using yes-no
questions or graphic indicators the patient could point to. Arguments
against patient-centered ventilation included the difficulty of properly
controlling increasingly complex ventilators, and the possibility of lung
damage in a subset of patients at risk for such problems. Another theme of
this session was improvement of dyspnea in palliative care situations, which
the moderator categorized as threee kinds: dyspnea only during exertion that
severely limits a person’s capacity to engage in daily life; paroxysmal
dyspnea that causes brief but very frightening episodic discomfort; and
sustained dyspnea that cannot be escaped even at rest. The clinicians
present agreed that current treatment options are limited, but that verbal
counseling, breathing training, and relaxation techniques could be very
useful in many circumstances if they are tailored to fit the case. In
addition, reconditioning may help those with dyspnea only on exertion, and
that opiates are a useful tool for sustained dyspnea, especially in the
final weeks of life. There was practical discussion about what can be done
to treat dyspnea when the ICU becomes a defacto palliative care unit, and
philosophical discussion about increasing priority on addressing the dyspnea
the patient feels, rather than fixating only on attempts to reverse the
pathophysiology.
One of the most important outcomes of this meeting was to foster
conversation between scientists who had very different orientations and
approaches to the study dyspnea. There was wide agreement that the group
should continue to meet periodically, and should open other channels of
communication as well. We have established a dyspnea interest group mailing
list that one can join by emailing dyspnea@hsph.harvard.edu. We profusely
thank our host: Sue Lowery, of the Biology Dept. at USD; and our sponsors:
IUPS, The Physiological Society, and especially Boehringer-Ingelheim
Pharmaceuticals who provided the bulk of the funding.
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