| Current
Respiratory Medicine Reviews
ISSN: 1573-398X
Current Respiratory Medicine
Reviews
Volume 3, Number 3, August 2007
Contents
Editorial Pp. 169
Expiratory High-Resolution CT in Diffuse Lung Diseases
Pp. 170-178
Hiroaki Arakawa
[Abstract]
Ventilatory Abnormalities During Exercise in Heart
Failure: A Mini Review Pp. 179-187
Ross Arena, Marco Guazzi and Jonathan Myers
[Abstract]
The Role of Anticoagulation in IPF Pp. 188-192
Geetika Verma, Matthew Binnie and Charles K.N. Chan
[Abstract]
Effects of Extracellular Matrix and Integrin Interactions
on Airway Smooth Muscle Phenotype and Function: It Takes Two
to Tango! Pp. 193-205
Thai Tran, Reinoud Gosens and Andrew J. Halayko
[Abstract]
Measurement of Extravascular Lung Water in Critically
Ill Patients Pp. 206-213
Samir G. Sakka
[Abstract]
Granulomatous Lung Disease. Disease for Pulmomologists:
Diagnosis and Treatment Pp. 214-220
Hidenobu Shigemitsu and Om P. Sharma
[Abstract]
Interstitial Lung Disease Associated with Polymyositis
Dermatomyositis Pp. 221-232
Toshinori Takada, Jun-ichi Narita, Eiichi Suzuki and Fumitake
Gejyo
[Abstract]
Respiratory Failure in Cancer Patients: Non-Infectious
Complications of Antineoplastic Agents for Solid Tumors
Pp. 229-232
Bobbak Vahid and Paul E. Marik
[Abstract]
Optimal Treatment of Severe Community-Acquired Pneumonia
Pp. 233-239
Grant W. Waterer and Marcos I. Restrepo
[Abstract]
Abstracts
[Back to top]
Editorial
[Back to top]
Expiratory High-Resolution CT in Diffuse Lung Diseases
Hiroaki Arakawa
High-resolution computed tomography (CT) of the lung is a
powerful diagnostic tool in revealing morphological abnormalities
that closely correspond to those of the pathological tissue
specimen. High-resolution CT is usually obtained at the end
of deep inspiration; however, additional CT obtained at the
end of deep exhalation (expiratory CT) provides a different
set of information. The lung usually shows a homogeneous increase
in lung density after forced exhalation, and the cross-sectional
area decreases accordingly in healthy subjects; however, those
areas peripheral to diseased airways often show no increase
in lung density or decrease in cross-sectional area after
exhalation. These areas (air-trapping areas) are seen in various
diffuse lung diseases, including small airway diseases, some
interstitial lung diseases, and even in normal subjects. Irrespective
of the disease or condition, the extent of air-trapping approximately
correlates with obstructive functional impairment. In patients
with suspected lung parenchymal disease, air-trapping can
be the only imaging abnormality; thus, expiratory CT can visualize
early or mild parenchymal lung disease before the development
of overt abnormalities.
In this manuscript, the various techniques of paired inspiratory
and expiratory high-resolution CT are reviewed and the normal
appearances of expiratory images are described. Correlation
of imaging findings with pulmonary function tests is discussed
and the clinical impact of the technique is reviewed for some
of the diffuse parenchymal lung diseases.
[Back to top]
Ventilatory Abnormalities During Exercise in Heart
Failure: A Mini Review
Ross Arena, Marco Guazzi and Jonathan Myers
Heart Failure (HF) is a significant health care concern with
in both the United States and Europe. While there are a number
of mechanisms that lead to HF, a decline in the response to
exercise is common amongst the various etiologies. Cardiopulmonary
exercise testing (CPET) is a well established diagnostic and
prognostic tool in the HF population. This exercise testing
technique allows for the measurement of oxygen consumption
(VO2), carbon dioxide production
(VCO2) and minute ventilation
(VE) across time. Cardiovascular and skeletal muscle dysfunction
is considered central to the often abnormal exercise response
observed in the HF population. As such, VO2
at peak exercise is the most recognized CPET variable in patients
with HF. In recent years, however, the importance of assessing
VE during exercise, either alone or in combination with expired
gases, has been highlighted in a number of investigations.
The VE-VCO2 relationship,
exercise periodic breathing (EPB) and the oxygen uptake efficiency
slope (OUES) are, to this point, the most studied CPET measurements
incorporating VE in the HF population. Of these, the VE-VCO2
relationship has received the greatest amount of attention.
This review will address the clinical significance of these
CPET measurements in the HF population.
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The Role of Anticoagulation in IPF
Geetika Verma, Matthew Binnie and Charles K.N. Chan
Idiopathic pulmonary fibrosis (IPF) is a disease with limited
therapeutic options. Corticosteroids and immunouppressive
agents have been the mainstays of treatment, primarily due
to their anti-inflammatory properties. However, they have
demonstrated minimal efficacy and significant toxicity. Recent
efforts have sought to target other aspects of the pathophysiology
of this condition. Several investigators have hypothesized
that imbalances of coagulation and fibrinolysis play a role
in the pathophysiology of IPF. Thrombin has been identified
as a possible trigger of fibroblast proliferation in IPF,
suggesting a role for thrombin inhibition in modifying the
course of disease. Furthermore, anticoagulation may have a
role in preventing thrombotic complications in IPF patients
with secondary pulmonary hypertension.
This review will discuss the potential role for anticoagulation
in the treatment of IPF. One randomised control trial has
demonstrated a significant survival benefit associated with
anticoagulation of IPF patients. We will review the evidence
supporting this treatment strategy, as well as its possible
mechanisms of action.
[Back to top]
Effects of Extracellular Matrix and Integrin Interactions
on Airway Smooth Muscle Phenotype and Function: It Takes Two
to Tango!
Thai Tran, Reinoud Gosens and Andrew J. Halayko
Alterations in the composition of the extracellular matrix
(ECM) and its abundance are important features of airway fibrosis,
which is observed in lung disorders such as asthma, COPD and
cystic fibrosis. The ECM was originally thought to only play
a passive, structural role by providing a stable framework
for the resident airway cells from which they are synthesized.
However, there is now increasing evidence that the ECM impacts
on the biological activity of smooth muscle cells, fibroblasts,
and epithelial cells. Current anti-asthma therapy is only
partially effective in preventing matrix deposition in chronic
asthma, and does not reverse established fibrosis. Little
is known about the signal transduction pathways that mediate
ECM effects on airway smooth muscle cells. Importantly, in
order for the ECM to influence myocyte phenotype and function,
the cell must possess selective receptors (integrins) to induce
intracellular signalling pathways. This mini-review explores
current knowledge of the role of the ECM and its receptors
(integrins) on airway smooth muscle phenotype and function
and highlights their possible importance in airway disease.
New signalling molecules that may be essential in mediating
ECM-integrin interactions will also be discussed as they may
prove to be novel targets for developing new therapies for
asthma.
[Back to top]
Measurement of Extravascular Lung Water in Critically
Ill Patients
Samir G. Sakka
In critically ill patients, capillary leakage often occurs
which in the lungs may lead to pulmonary edema by increased
microvascular pressure and permeability. However, clinical
assessment of the extent of pulmonary capillary leakage and
pulmonary edema is difficult. Several decades ago, the transpulmonary
double indicator (thermo-dye) dilution technique has been
introduced for quantification of extravasastion of fluids
in the lungs by determination of the extravascular lung water
(EVLW). The thermo-dye is based on simultaneous central venous
injection of a freely diffusible indicator (‘cold’)
and a plasma-bound indicator (indocyanine green). This technique
has been extensively validated in animal experiments using
post-mortem gravimetry and in humans using radionuclide techniques.
However, the thermo-dye dilution technique is relatively expensive
and time consuming therefore assessment of EVLW is increasingly
performed by single transpulmonary thermodilution, which according
to animal experimental and clinical studies is sufficiently
accurate for estimation of EVLW. Using EVLW to guide the management
of patients with both cardiac and non-cardiac pulmonary edema
(ARDS) has been shown to reduce the duration of mechanical
ventilation, length of stay in the intensive care unit and
potentially intensive care costs. EVLW-guided therapy also
reduced mortality in those patients with congestive heart
failure and ARDS. Recent clinical studies have shown that
in critically ill patients EVLW correlates with the severity
of lung injury and that it does have a prognostic value. Thus,
monitoring EVLW can be a useful additional tool in the goal-directed
therapy of critically ill patients, especially those with
severe sepsis and sepsis-induced acute lung injury.
[Back to top]
Granulomatous Lung Disease. Disease for Pulmomologists:
Diagnosis and Treatment
Hidenobu Shigemitsu and Om P. Sharma
Granuloma, a collection of various inflammatory cells composed
of lymphocytes, epithelioid cells, giant cells, mononuclear
cells, eosinophils, plasma cells, and fibroblasts is a host
response to an antigen(s). Specific patterns of the granulomatous
response such as necrosis, caseation, and the presence or
absence of microorganisms or foreign bodies aid in securing
the diagnosis. The common causes of granulomatous lung disease
include sarcoidosis, hypersensitivity pneumonitis, Wegener’s
granulomatosis, mycobacterial infections, fungal diseases,
parasitic infestations, and drugs. This review, designed for
practicing pulmonologists, emphasizes diagnosis and treatment
of some of the common pulmonary granulomas.
[Back to top]
Interstitial Lung Disease Associated with Polymyositis
Dermatomyositis
Toshinori Takada, Jun-ichi Narita, Eiichi Suzuki and Fumitake
Gejyo
Polymyositis and dermatomyositis (PM-DM) are forms of idiopathic
inflammatory myositis. Interstitial lung disease (ILD) in
PM-DM is recognized as a serious complication and a major
cause of death in this disease. According to the results of
immunophenotyping of lymphocytes in bronchoalveolar lavage
fluid, cytotoxic T lymphocytes may be major pulmonary inflammatory
cells of ILD in PM-DM. Glucocorticoids are considered the
first-line drug treatment for PM-DM patients with ILD, however
they are often not sufficient to obtain improvement of ILD
as a single agent. Furthermore, the addition of immunosuppressive
drugs becomes necessary as steroid sparing agents to avoid
the severe side-effects often seen with high-dose steroid
treatment. Cyclophosphamide, cyclosporin, and tacrolimus were
reported to be effective in treatment of refractory ILD in
PM-DM. Although other immunosuppressive agents; mycophenolate
mofetil, intravenous immunoglobulin, and anti-TNF agents have
appeared as promising agents for refractory PM-DM, the efficacy
on ILD in PM-DM is still unknown. Even if treatment is initiated
early in the course of the disease, some patients still develop
irreversible fatal lung fibrosis under aggressive immunosuppressive
therapy. The fastest way to find the most effective treatment
may be to investigate the pathogenesis of the disease in detail
before initiation of immunosuppressive therapy including glucocorticoids.
[Back to top]
Respiratory Failure in Cancer Patients: Non-Infectious
Complications of Antineoplastic Agents for Solid Tumors
Bobbak Vahid and Paul E. Marik
Chemotherapy-induced respiratory failure is being increasingly
recognized as a cause of respiratory failure in the intensive
care unit. The frequency of chemotherapy-induced respiratory
failure is low, however with increasing number of patients
receiving new chemotherapeutic agents more cases can be expected
to be seen. Chemotherapy-induced respiratory failure can be
due to bronchospasm and hypersensitivity reactions, pulmonary
hemorrhage, interstitial pneu-monitis, eosinophilic pneumonia,
and non-cardiogenic pulmonary edema. Pulmonary and critical
care physicians should be aware of the clinical presentation
of chemotherapy-induced respiratory failure.
[Back to top]
Optimal Treatment of Severe Community-Acquired Pneumonia
Grant W. Waterer and Marcos I. Restrepo
Community-acquired pneumonia (CAP) is associated
with significant morbidity and mortality and is the most common
cause of death from infectious diseases. Severe CAP (SCAP)
patients that required ICU admission carry the highest mortality
rates. Multiple sets of clinical practice guidelines have
been published in the past few years addressing the treatment
of CAP, and they all agree that CAP patients admitted to the
hospital represent a major concern, and appropriate empiric
therapy should be instituted to improve clinical outcomes.
The purpose of this article is to review the current literature
regarding the optimal empiric selection of antibiotic therapy
for patients with SCAP. In addition emphasis on the empiric
and direct therapy will be made on patients with bacteremic
pneumococcal pneumonia.
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