Pulmonary Disease
Diseases that result in fewer alveoli and/or deflation of the alveoli are
quite serious. Such conditions are common causes of inadequate
oxygenation of the blood and frequently result in disability and death.
Among such conditions are chronic lung diseases such as
bronchopulmonary dysplasia (BPD), idiopathic pulmonary fibrosis (IPF),
asthma, and some disorders covered by the global term, chronic
obstructive pulmonary disease (COPD) such as emphysema.
Bronchopulmonary dysplasia (BPD)
BPD is a disease of prematurely born infants, and is characterized mainly
by a failure to form a sufficient number of appropriately sized alveoli.
The body has no natural way to repair this and, therefore, BPD is a
chronic disease that affects sufferers all through their life. According to
the National Heart, Lung, Blood Institute at the National Institutes of
Health (NIH) between 5,000 and 10,000 cases of BPD occur every year
in the US, with an overall annual cost of treatment for this chronic disease
that approaches $2.4 billion.
Asthma
Asthma is a life-threatening lung disease in which airways become
inflamed, leading to breathing difficulties (eg, wheezing, shortness of
breath). Asthma prevalence has been increasing since the early 1980s in
all ages and racial groups, and in both sexes. According to the Centers
for Disease Control and Prevention, the number of asthma sufferers more
than doubled from 6.7 million cases in 1980 to 17 million cases in 1998.
According to the National Heart, Lung, and Blood Institute, direct and
indirect financial costs for all forms of asthma total $14 billion in the US,
including $9.4 billion in direct costs and $4.6 billion in indirect costs
such as missed work or school days.
Chronic Obstructive Pulmonary Disease and Emphysema
Chronic Obstructive Pulmonary Disease (COPD) is a slowly-progressive
disease of the characterized by gradual loss of lung function. COPD
encompasses a wide variety of disorders, including chronic bronchitis,
chronic asthma, emphysema, bronchiectasis, immunoglobulin deficiency,
and cystic fibrosis. Although the vast majority of COPD cases consist of
chronic bronchitis and emphysema, several of these disorders often co-
exist in the same patient. Originally, the classical definition of COPD did
not include “fibrosis” of the lung as a key manifestation of these
disorders, but it is now known that fibrotic changes in the lungs are
associated with many COPD conditions. Emphysema, a disease of
middle and advanced age, appears to be due to progressive destruction of
alveoli that may be protease-mediated. About 3 million Americans have
been diagnosed with this type of COPD disorder, and this disease is
associated with more than $2.5 billion in annual health care expenses. In
addition, emphysema causes or contributes to 100,000 deaths in the US
each year.
Idiopathic pulmonary fibrosis
Idiopathic (referring to a disease whose cause is not well-understood)
pulmonary fibrosis or IPF is a disease of inflammation that results in
fibrosis, or scarring of the lungs. In time, this fibrosis can build up to the
point where the lungs are unable to provide oxygen to the tissues of the
body. Equal numbers of men and women get the illness and most cases of
IPF are diagnosed when the patients are between the ages of 40 and 70.
As IPF progresses, the alveoli become damaged and scarred, resulting in
a stiffening of the lungs. There are more than 60,000 patients suffering
from IPF worldwide. A recent survey has suggested a prevalence of 1 in
5,000 (of which 3% to 4% may be familial).
The most compelling hypothesis for the pathogenesis of pulmonary
fibrosis is the protease/antiprotease theory. This theory is based on the
observation that airway irritants cause an influx of inflammatory cells in
the lung. These cells release a variety of proteases, including neutrophil
elastase, trypsin, and cathepsins which overwhelm the protective
antiprotease capacity of the lung. These enzymes are then free to weaken
the elastic and structural elements in the lung parenchyma. In support of
this theory, it has been discovered that the cytokine profile seen in
chronic obstructive pulmonary disease (COPD) is different from that
observed in asthma, with a higher level of cytokines known to be
associated with fibrosis in patients with emphysema and other COPD
subtypes.
Many of the diseases described above are characterized by abnormal
fibrosis in the lung which may be caused by a conversion (differentiation)
of the connective tissue from the “normal phenotype” lipofibroblasts in
the connective tissue to the “scarring phenotype” myofibroblasts. The
scientific founders of LINC have discovered a decrease in the amount of
a natural hormone-like protein modulator at the onset of fibrosis, a
discovery that can be used to develop diagnostic tools to monitor disease
progression (and to adjust ventilation systems to minimize damaging
trauma to the lungs). In addition, these investigatory have found that
replacing this protein (or by modulating one of the down-stream steps)
appears to arrest the fibrotic scarring process, providing a new
opportunity to develop effective therapeutics for these poorly treated
conditions.
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