| Current
Respiratory Medicine Reviews
ISSN: 1573-398X
Current Respiratory Medicine
Reviews
Volume 2, Number 2, May 2006
Contents
Editorial Pp.99-100
The Epithelial Cell in Lung Health and Emphysema Pathogenesis
Pp. 101-142
Becky A. Mercer, Vincent Lemaître, Charles A. Powell
and Jeanine D’Armiento
[Abstract]
Role of CD38 in Airway Function Pp. 143-156
Bit Na Kang, Alonso G.P. Guedes, K.G. Tirumurugaan, Joseph
A. Jude, Deepak A. Deshpande, Reynold A. Panettieri, Yassine
Amrani, Frances E. Lund, Timothy F. Walseth and Mathur S.
Kannan
[Abstract]
The Role of Coagulation and Fibrinolysis in the Pathogenesis
of Acute Lung Injury Pp. 157-171
J.A. Bastarache, L. Wang and L.B. Ware
[Abstract]
A Review of Epidemiological Evidence on Short-Term
Effects of Environ-mental Factors on Respiratory Prob-lems
in Children Pp. 173-181
Cristina Linares Gil, Julio Díaz Jiménez,Aurelio
Tobías Garcés and Ángel Otero Puime
[Abstract]
Potential Utility of Mycobacterium w Vaccine
in Control of Tuberculosis Pp. 183-188
Murli L. Mathur
[Abstract]
Non-Invasive Assessment of Airway Inflammation in
Asthma: An Overview Pp. 189-196
D.E. Shaw and I.D. Pavord
[Abstract]
Factors Influencing Individual Variability in the
Therapeutic Response to Corticosteroids in Asthma Pp.
197-209
Mark Spears and Neil C. Thomson
[Abstract]
Nebulizer Therapy in Pulmonology: Review of the Literature
Pp. 211-235
Andrea S. Melani and Letizia S. Bracci
[Abstract]
Home Oxygen Therapy for the 21st
Century Pp. 237-251
Christian Domingo
[Abstract]
Abstracts
[Back to top]
Editorial
Long-Term Oxygen Therapy: From “Oxygen-Bars”
to Home Oxygen Therapy
Sandalwood, wintergreen, cranberry, mocha mint, peppermint.
New breath mint flavors? New smoothie flavors? No they are
flavors of the oxygen offered at oxygen bars across the World.
This is a new trend that started among the night clubs in
1990s, since its introduction has caught on, and customers
pile up to get this trendy oxygen therapy with the false assumption
that they will benefit from it.
The therapeutic use of oxygen was pioneered in the early 20th
century by the respiratory physiologist John Scott Haldane
[1]. He became aware of its therapeutic effects on carbon
monoxide poisoning, and was also an advocate of oxygen as
a therapeutic agent in other respiratory illness. In 1922,
the concept of modern oxygen therapy was introduced by Alvin
Barach and since then its use has grown widely [2]. Understanding
the effects of hypoxemia and their reversal with oxygen supplementation
has made it a common practice [3]. In this issue of Current
Respiratory Medicine Reviews, Domingo expands on our
understanding of the therapeutic use of oxygen [4].
Long- term oxygen therapy (LTOT) has become standard part
of the armamentarium for the treatment of hypoxemic patients
with chronic obstructive pulmonary disease (COPD) [5]. In
the United States, is estimated that there are 800,000 patients
receiving LTOT therapy. Patients who require LTOT have significantly
greater annual health care costs than otherwise-similar patients
who do not require oxygen therapy [6].
Even though several randomized, controlled trials have tried
to demonstrate that LTOT in patients with interstitial lung
disease have a beneficial survival effect, they have failed
to prove it [7]. On the other hand, it is clear that LTOT
improves both the length and the quality of life for patients
with chronic hypoxemia and chronic obstructive pulmonary disease
(COPD). The improvement in survival with LTOT seems to be
proportional to the number of hours of therapy [8]. In patients
with hypoxemia, LTOT has shown to improve survival, improving
pulmonary hemodynamics and to reduce cardiac work [3]. In
patients with airflow obstruction, LTOT increases the distance
patients can walk increasing oxygen delivery and its utilization
by muscles during exercise [9]. Even though the desire to
decrease the work of breathing is not an accepted indication
for LTOT, the use of it decreases minute ventilation and subsequently
oxygen cost of breathing, helping as well improving one of
COPD major symptoms: dyspnea. As noted in the article by Domingo,
LTOT is considered safe and is associated with relatively
few side effects [4]. Maybe that is the main reason as to
why there has been an explosion of “oxygen bars”
across the world. This false sense of security has propagated
these “bars” in which customers can choose a “flavor”
of oxygen to inhale and obtain the “beneficial effects”.
The use of oxygen, however, needs to be well understood. Identifying
the patient that will benefit of LTOT is a very important
task that requires a full assessment of the patient and its
environment. For LTOT to be successful patient compliance
is essential. Patient compliance can be improved by initial
and ongoing patient education and by ensuring patient access
to appropriate LTOT services, systems and choices that best
meet their medical needs.
Clearly there are many benefits of oxygen for pulmonary patients
and articles such as the one written by Domingo are important
for clinicians dealing with patients requiring oxygen supplementation
and hoping to avoid the “hype” of oxygen bars!
REFERENCES
[1] Sternbach GL, Varon J. The discovery and rediscovery of
oxygen. J Emerg Med 2005; 28: 221-4.
[2] Barach AL. The therapeutic use of oxygen. JAMA 1922; 79:
693-8.
[3] Tarpy SP, Celli BR. Long term oxygen therapy. N Engl J
Med 1995; 333: 710-4.
[4] Domingo C. Home oxygen therapy for the 21st
century. Curr Respir Med Rev 2006; 2: 237-51.
[5] Eaton T, Lewis C, Young P, et al. Long term oxygen
therapy improves health-related quality of life. Respir Med
2004; 98: 285-93.
[6] O’Donohue WJ Jr, Plummer AL. Magnitude of usage
and cost of home oxygen in the United States. Chest 1995;
107: 301-2.
[7] Crockett AJ, Cranston JM, Antic N. Domiciliary oxygen
for interstitial lung disease. Cochrane Database Syst Rev
2001; 3. CD002883.
[8] Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal
oxygen therapy in hypoxemic chronic obstructive pulmonary
disease. Ann Intern Med 1985; 102: 29-36.
[9] Morrison DA, Stovall JR. Increased exercise capacity in
hypoxemic patients after long-term oxygen therapy. Chest 1992;
102: 542-50.
Pilar Acosta Joseph Varon
(Editor-in-Chief)
2219 Dorrington Street
Houston
Texas 77030
USA
E-mail: Joseph.Varon@uth.tmc.edu
Pilar Acosta
Facultad de Medicina de Tampico
Tampico
Mexico
[Back to top]
The Epithelial Cell in Lung Health and Emphysema Pathogenesis
Becky A. Mercer, Vincent Lemaître, Charles A. Powell
and Jeanine D’Armiento
Cigarette smoking is the primary cause of the irreversible
lung disease emphysema. Historically, inflammatory cells such
as macrophages and neutrophils have been studied for their
role in emphysema pathology. However, recent studies indicate
that the lung epithelium is an active participant in emphysema
pathogenesis and plays a critical role in the lung’s
response to cigarette smoke. Tobacco smoke increases protease
production and alters cytokine expression in isolated epithelial
cells, suggesting that these cells respond potently even in
the absence of a complete inflammatory program. Tobacco smoke
also acts as an immunosuppressant, reducing the defense function
of airway epithelial cells and enhancing colonization of the
lower airways. Thus, the paradigm that emphysema is strictly
an inflammatory-cell based disease is shifting to consider
the involvement of resident epithelial cells. Here we review
the role of epithelial cells in lung development and emphysema.
To better understand tobacco-epithelial interactions we performed
microarray analyses of RNA from human airway epithelial cells
exposed to smoke extract for 24 hours. These studies identified
differential regulation of 425 genes involved in diverse biological
processes, such as apoptosis, immune function, cell cycle,
signal transduction, proliferation, and oxidant defense. Some
of these genes, including VEGF, glutathione peroxidase, IL-13
receptor, and cytochrome P450, have been previously reported
to be altered in the lungs of smokers. Others, such as pirin,
cathepsin L, STAT1, and BMP2, are shown here for the first
time to have a potential role in smoke-associated injury.
These data broaden our understanding of the importance of
epithelial cells in lung health and cigarette smoke-induced
emphysema.
[Back to top]
Role of CD38 in Airway Function
Bit Na Kang, Alonso G.P. Guedes, K.G. Tirumurugaan, Joseph
A. Jude, Deepak A. Deshpande, Reynold A. Panettieri, Yassine
Amrani, Frances E. Lund, Timothy F. Walseth and Mathur S.
Kannan
CD38, a 45-kDa cell surface glycoprotein, is involved in
the synthesis of the calcium mobilizing second messenger molecule
cyclic ADP-ribose. Cyclic ADP-ribose is known to release calcium
from the sarcoplasmic reticulum of airway smooth muscle cells.
The pharmacological features of cyclic ADP-ribose-mediated
calcium release in airway smooth muscle cells are distinct
from those mediated by inositol 1,4,5-trisphosphate and involve
activation of ryanodine receptor channels. In airway smooth
muscle cells, contractile agonists recruit cyclic ADP-ribose
for intracellular calcium release in a receptor- and receptor-subtype-specific
fashion. The CD38/cyclic ADP-ribose signaling has a role in
airway function, since methacholine-induced airway resistance
is significantly lower in CD38 deficient mice than in the
wild type controls. The diminished airway responsiveness appears
to result from lower intracellular calcium responses to spasmogens.
In human airway smooth muscle cells, inflammatory and Th-2
cytokines increase the expression of CD38 and augment the
capacity for cyclic ADP-ribose-mediated calcium release during
agonist stimulation. These results suggest a role for cyclic
ADP-ribose in airway smooth muscle hyperresponsiveness during
inflammation. This review will focus on the role of CD38 and
cyclic ADP-ribose in normal airway function and its potential
contribution to airway hyperresponsiveness in inflammatory
diseases such as asthma.
[Back to top]
The Role of Coagulation and Fibrinolysis in the Pathogenesis
of Acute Lung Injury
J.A. Bastarache, L. Wang and L.B. Ware
Acute lung injury (ALI) and acute respiratory distress syndrome
(ARDS) are common and life threatening causes of acute respiratory
failure throughout the world. Much is known about the pathogenesis
of this devastating problem yet specific pharmacologic therapies
are lacking. In recent years many investigators have demonstrated
that the alveolar compartment in ALI/ARDS is a pro-coagulant,
anti-fibrinolytic environment. With the clinical success of
modulation of coagulation abnormalities in severe sepsis with
administration of Drotecogin alfa (activated protein C), the
importance of the coagulation in the pathogenesis of human
disease is becoming clear. In this full length review we will
summarize the current literature in the field of coagulation
and fibrinolytic abnormalities in acute lung injury (ALI)
and acute respiratory distress syndrome (ARDS). We will focus
on both in vitro and in vivo studies
of the role of the coagulation cascade in lung injury at the
level of initiation of coagulation through modulation of tissue
factor (TF) and tissue factor pathway inhibitor (TFPI), propagation
of coagulation via protein C and thrombomodulin (TM),
and resolution through thrombolysis by plasminogen activator
(PA), plasminogen activator receptor (PAR) and plasminogen
activator inhibitor-1 (PAI-1). We will highlight some of our
own work in this field as well as discuss important contributions
from other laboratories. In addition, we will discuss the
relevant cell studies that may potentially lead to new therapies.
[Back to top]
A Review of Epidemiological Evidence on Short-Term
Effects of Environ-mental Factors on Respiratory Prob-lems
in Children
Cristina Linares Gil, Julio Díaz Jiménez,Aurelio
Tobías Garcés and Ángel Otero Puime
A growing body of evidence has demonstrated that children
are more vulnerable than adults to environmental factors because
children are growing and their rapidly developing organ systems
are particularly vulnerable. Between the burden of environmental
risks that children are exposed to, outdoor air pollution
is one of the main factors responsible of their respiratory
health. Evidence for effects of air pollution on children
has been rising and its effects are seen at concentrations
that are common today. Although the role of air pollution
in exacerbating existing illness as bronchitis or pneumonia
has been well known, recent evidence has implicated pollution
exposure with the development of asthma and atopy in children.
On the other hand, little attention has been paid yet to the
role of another environmental factors as pollen concentrations
and urban noise levels over children health, which effects
require additional investigation. About noise, recent studies
suggest that the combined effects of chronic exposure to traffic
related air pollution and noise upon the risk of respiratory
diseases in children.
[Back to top]
Potential Utility of Mycobacterium w Vaccine
in Control of Tuberculosis
Murli L. Mathur
Mycobacterium w is a non-pathogenic, saprophytic,
atypical mycobacterium with the ability to produce macrophage
activating factors from lymphocytes of human patients. Prior
immunization with heat-killed suspension of Mycobacterium
w shows protection against sub-lethal infection with
Mycobacterium tuberculosis H37Rv in mice. Heat-killed
Mycobacterium w vaccine is manufactured
by M/s Cadila Pharmaceuticals, Ahmedabad, India. Combined
heat-killed M. w vaccine and multidrug treatment
(MDT) revealed clinical, histological and bacteriological
improvements in highly bacillated untreated anergic lepromatous
cases of leprosy. In healthy contacts of leprosy patients,
M. w vaccine has shown lepromin conversion and protection
against leprosy. Only a few clinical studies have been carried
out using antituberculous treatment with and without M.
w vaccine in pulmonary tuberculosis, in which faster
sputum conversion and higher cure rate have been observed
in M. w group. M. w vaccine has shown potential
of Tuberculin conversion in HIV positive subjects. In a study,
five monthly doses of M. w vaccine have shown highly
significant increase in CD4 count in HIV positive human beings.
More clinical trials are needed to confirm beneficial role
of M. w vaccine as an immunomodulator in therapy
and prevention of tuberculosis, particularly so in multidrug
resistant tuberculosis and those with HIV infection.
[Back to top]
Non-Invasive Assessment of Airway Inflammation in
Asthma: An Overview
D.E. Shaw and I.D. Pavord
The goals of asthma management are the accurate diagnosis
and effective control of symptoms, prevention of exacerbations
and the achievement and preservation of best pulmonary function.
Despite improvements in asthma care patients are still misdiagnosed
or undertreated. The reason for this is simple, asthma is
a heterogeneous disease, but in most primary and secondary
care settings only one facet, variable airflow obstruction,
is addressed. The two other main aspects of asthma, airway
inflammation and airway hyperresponsiveness, remain under-utilized
in both diagnosis and treatment of asthma. Treatment algorithms
based on airway hyperresponsiveness have been successfully
used to reduce asthma exacerbations but at the expense of
more corticosteroid use. Using a non-invasive marker of airway
inflammation has also been shown to reduce exacerbations compared
with a control group following current guidelines, but with
similar steroid dose between both groups and with comparative
symptom and quality of life measures.
There are various non-invasive markers of airway inflammation
(as opposed to bronchial biopsy and bronchoalveolar lavage).
This article will concentrate on the use of the two most clinically
important methods of assessing airway inflammation, namely
induced sputum and exhaled nitric oxide. It will evaluate
the indications, practicalities and use for each method and
discuss future areas for research.
[Back to top]
Factors Influencing Individual Variability in the
Therapeutic Response to Corticosteroids in Asthma
Mark Spears and Neil C. Thomson
Corticosteroids are the most effective treatment for asthma
but the therapeutic response varies markedly between individuals.
Multiple factors including genetic, environmental, asthma
related and concordance are likely to contribute to the heterogeneous
response to corticosteroids. Genetic variations at the level
of the glucocorticoid receptor have not been implicated to
date, but polymorphisms of TBX21 and corticotrophin-releasing
hormone receptor 1 genes are associated with enhanced efficacy
to inhaled corticosteroids. Cigarette smoking is an important
cause of insensitivity to corticosteroids. Mechanisms of corticosteroid
insensitivity in smokers with asthma are currently unexplained,
but could be due to alterations in airway inflammatory cell
phenotypes, changes in glucocorticoid receptor α
to β
ratio, and/or reduced histone deacetylase activity. Exposure
to allergens, infections and neutrophilic airway inflammation
as well as race and the rare phenotype of corticosteroid resistant
asthma are implicated in reduced efficacy. Poor concordance
with treatment is of particular importance. Management involves
advice on smoking cessation for smokers, assessment of concordance
and inhaler technique, review of delivery of care and step
up in treatment only after these issues have been addressed.
In the future, corticosteroid treatment might be guided by
pharmacogenetic assays and the use of alternative or additional
drugs for specific corticosteroid insensitive groups such
as smokers with asthma.
[Back to top]
Nebulizer Therapy in Pulmonology: Review of the Literature
Andrea S. Melani and Letizia S. Bracci
The lung is a very attractive target for drug delivery. Currently,
as direct access for the treatment of lower respiratory diseases.
Possibly, in the future, as the route of administration for
systemic therapies. Nebulizers are widely used throughout
the world in adult and padiatric medical practice. They are
used for the management of acute bronchoconstriction both
at home and in hospital, but also for long-term home treatment
of various lower respiratory diseases, mainly in elderly and
in infants. Overall, bronchodilators are the first class of
drugs used by nebulization. The efficiency of the nebulizer
has to be assured mainly for suspension, such as corticosteroids,
and hyperviscous solution, such as antimicrobials, which aerolize
with more difficulties with respect to bronchodilators. Unfortunately,
knowledge on the optimal use of nebulizers is limited. Guidelines
on best nebulizer practice are often lacking. There is a need
to establish some guidance for both the drug and nebulizer
manufacturers and prescribing physicians for optimization
of nebulizer therapy, individuating not only drugs, dosing
and administration schedule, but also the effective nebulizer
system and the method for its optimal use and maintenance.
[Back to top]
Home Oxygen Therapy for the 21st
Century
Christian Domingo
Oxygen was first identified at the end of the eighteenth
century but was not used as a therapeutic tool until 1887,
by Holsapel. Although oxygen toxicity has been reported, tolerance
of long-term oxygen therapy (LTOT) is excellent. In 1979,
for the first time, Neff and Petty observed that LTOT increased
life expectancy. In the early 1980s two randomized studies
(the NOTT and the MRC trial) established the clinical and
hemodynamic benefits of LTOT, and their findings were later
supported by other studies; recently, however, it has been
noted that the hemodynamic benefits do not last more than
two years. Polycythemia and neuropsychological functions have
also been found to improve with LTOT. Quality of life seems
to be affected in females but not in males. A first attempt
to establish recommendations for LTOT was made at the Denver
meeting in 1987, and this was followed by the publication
of more guidelines by lung societies in various countries.
In addition to the classic nasal prongs and facial masks,
new oxygen delivery devices allowing a 50% oxygen saving were
introduced: the transtracheal catheter and the nasal cannula
with reservoir and oxygen-conserving valve, which combined
with liquid oxygen, increased patients’ ambulatory activities
(including traveling) and improved hemodynamic parameters.
Gray areas of LTOT include nocturnal or diurnal desaturation
during effort but with daily Pa02 > 60 mm Hg at rest.
|
