Diffuse Lung Disease
David Turner, M.D.
I. Clinical Evaluation of the Chest Radiograph
A. Radiographic patterns
1.
Interstitial - reticulonodular
a.
Known cause - inorganic dust (pneumoconiosis), organic dust
(hypersensitivity pneumonitis), iatrogenic (drugs, radiation
therapy)
b.
Unknown cause - sarcoidosis, idiopathic pulmonary fibrosis,
pulmonary fibrosis with connective tissue disease
2.
Alveolar - fluffy, often with air bronchograms
a.
Acute - cardiogenic pulmonary edema, non-cardiogenic
pulmonary edema (ARDS), diffuse alveolar pneumonia, alveolar
hemorrhage
b.
Subacute or chronic - sarcoidosis, bronchioloalveolar cell
carcinoma, lymphoma, pulmonary alveolar proteinosis,
desquamative interstitial pneumonitis
3.
Nodular - often suggests hematogenous origin
a. Disseminated malignancy, tuberculosis, fungal disease,
pneumoconiosis, sarcoidosis, eosinophilic granuloma
B. Distribution of disease
1.
Lower lobe - idiopathic pulmonary fibrosis, pulmonary fibrosis
associated with connective tissue disease, asbestosis
2.
Upper lobe - silicosis, sarcoidosis, eosinophilic granuloma
3.
Non-anatomic margins - radiation-induced pulmonary disease
4.
Peripheral distribution - chronic eosinophilic pneumonia;
occasionally bronchiolitis obliterans with organizing pneumonia
C. With hilar adenopathy - sarcoidosis, silicosis, berylliosis, malignancy
D. With pleural disease - asbestosis, RA, lupus, occasionally sarcoidosis. In
AIDS, suggestive of KS.
It is important to recognize that when we are faced with a patient with diffuse lung
disease there are several radiographic patterns. It is often useful to separate out 3 types
of radiographic patterns. First of all an interstitial pattern, often called reticulonodular.
Secondly there is an alveolar pattern, and thirdly there is a nodular pattern.
The interstitial pattern or reticulonodular pattern is characterized by a lot of lines, dots,
and streaks. There are about 150 different disorders that can produce this type of
pattern. That makes it very difficult to create a realistic sort of differential diagnosis. I
think when approached with this type of radiograph the best thing is to try to break
down the long differential diagnosis. I find it is easiest to break it down into 3
categories. First of all, diseases of known cause, second of all, diseases of unknown
cause, and third, mimicking causes, or causes that look like interstitial lung disease but
in fact really fall out of the diagnostic category of what we usually consider in this broad
group of disease. Under each of these 3 categories there are 3 separate sub-categories.
For example, disease of known cause is inorganic dust, organic dust, and iatrogenic.
Within the iatrogenic ones would be things such as drugs and radiation therapy. The
drugs include cancer chemotherapeutic agents. Disease of unknown cause is sarcoidosis,
idiopathic pulmonary fibrosis, and pulmonary fibrosis associated with connective tissue
disease. The mimicking causes are congestive heart failure, malignancy, and infections,
and of the infections, particularly viral pneumonia and Pneumocystis carinii pneumonia.
When faced with a patient that has this type of interstitial pattern, it is actually
worthwhile to go first to the 3rd cause, the mimicking causes and make sure that your
not dealing with someone who might have heart failure, tumor, or infection.
The second category is an alveolar pattern, and, unlike the interstitial pattern, this is a
pattern that is more fluffy, cloudlike, or cottony and represents filling of alveolar spaces
with fluid or an inflammatory infiltrate often. With the alveolar lung diseases I think it
is actually best to separate out 2 types of presentation either an acute presentation or a
subacute or chronic presentation. With an acute presentation the easiest way to
categorize of characterize alveolar lung disease is by thinking about the types of the
things that can fill alveolar spaces. For example, we can have a relatively low protein or
transudative type of fluid as we might see in a patient with cardiogenic pulmonary
edema. We can see more of a relatively high protein fluid due to abnormal permeability
of the alveolar epithelium as we might see in the acute respiratory distress syndrome.
Inflammatory fluid can occur in diffuse alveolar pneumonia, and we can have blood
with diffuse alveolar hemorrhage. The subacute or chronic disorders that can fill
alveolar spaces. Those include sarcoidosis, bronchioloalveolar cell carcinoma,
lymphoma, alveolar proteinosis, and DIP or desquamative interstitial pneumonitis.
The 3rd radiographic pattern is a pattern of nodular lung disease and these discrete
nodules. This is actually from a patient with disseminated cancer. I should mention that
the interstitial pattern was from scleredema interstitial lung disease. The diffuse alveolar
pattern was from acute respiratory distress syndrome. This one though is from a patient
who has disseminated carcinoma. For nodular lung disease, often what we are thinking
about are disorders that spread to the lung by hematogenous spread. For example,
disseminated malignancy or some of the granulomatous diseases when there has been
spread of the organism to the lung that has resulted from hematogenous spread.
Disseminated malignancy, tuberculosis, and fungal disease are examples of this.
However, there are some disorders that actually can produce a nodular pattern because
of airway access to the lung such as the pneumoconiosis, the inhaled dust disorders.
Then there are a couple of idiopathic disorders, like sarcoidosis and eosinophilic
granuloma, that can produce nodular lung disease. One point to keep in mind is that
sarcoidosis falls into all 3 categories, so sarcoid can produce an interstitial pattern, an
alveolar pattern, and a nodular pattern.
The distribution of disease, and by this I mean radiographic distribution of disease
where it is in the lungs, can actually be very helpful as one try’s to put together the
differential diagnosis. For example, lower lobe disease is relatively common in
idiopathic pulmonary fibrosis, pulmonary fibrosis associated with connective tissue
disease, or asbestosis related. In contrast, upper lobe disease is seen with silicosis,
sarcoidosis, and eosinophilic granuloma. If we see margins that are non-anatomic and
by that I mean relatively sharp margins that do not follow the distribution of lobar
II.
Diagnosis and Treatment of Diffuse Lung Disease
A. Idiopathic pulmonary fibrosis (IPF)
1.
Original description of Hamman-Rich syndrome was an acute
interstitial pneumonia with rapid progression and death within
months; this is different from chronic idiopathic pulmonary fibrosis
2.
Desquamative interstitial pneumonia (DIP) - not clear if a subtype of
IPF, a cellular variant of IPF, or a different disease. Desquamated
cells are primarily alveolar macrophages
a.
Respiratory bronchiolitis in smokers may be associated with
interstitial lung disease resembling DIP; ? part of a spectrum,
since large majority of patients with DIP are also smokers
3.
Therapy
a.
Standard therapy is still prednisone
b.
Increasing interest in cyclophosphamide or azathioprine
used instead of, or in conjunction with steroids, but relative
role of steroids and other immunosuppressives is not yet
clear
B. Sarcoidosis
1. Despite common finding of depressed cell-mediated immunity with
cutaneous anergy, cell-mediated immune processes are enhanced
locally in the lung
a. Bronchoalveolar lavage - increased lymphocytes with
increased CD4/CD8 ratio
2.
Pattern of parenchymal infiltrates on chest X-ray can be
reticulonodular, nodular, or alveolar
3.
Endobronchial involvement can cause chronic cough and/or airflow
obstruction
4.
Angiotensin converting enzyme levels - generally not useful for
diagnosis or for following disease activity
5.
Standard treatment is still corticosteroids; results with cyclosporine
have been disappointing. ? role for methotrexate.
C. Hypersensitivity pneumonitis
1.
Examples - farmer's lung; air conditioner or humidifier lung
2.
Pathology shows mononuclear cell infiltrate with poorly formed
granulomas
3.
Distinction between acute hypersensitivity pneumonitis (fever,
cough, dyspnea, pulmonary infiltrates hours after exposure) and
chronic hypersensitivity pneumonitis (mimics other forms of
chronic interstitial lung disease)
boundaries or fissures then we will often think about something like radiation
pneumonitis or radiation fibrosis, which often tends to follow the ports of the radiation
therapy. Finally a peripheral pattern and I will show you an example of this later where
the infiltrates are primarily along the periphery of the lung is seen in chronic
eosinophilic pneumonia and sometimes in bronchiolitis obliterans with organizing
pneumonia.
Associated features on the radiograph may be helpful if there is hilar adenopathy we
tend o think of sarcoid, silicosis, berylliosis, and malignancy. Silicosis and berylliosis
are the 2 inhaled disorders for pneumoconiosis that can be associated hilar adenopathy.
If we see associated pleural disease then obviously asbestosis, a couple of the connective
tissue diseases particularly rheumatoid arthritis and lupus and occasionally with sarcoid,
although less than 10% of patients with sarcoid will have involvement of the pleural. In
a patient who has AIDS and has pleural disease then we often think about coexisting
Kaposi sarcoma or Kaposi sarcoma really is the cause of the pleural disease particularly
pleural effusion.
A few points about the pulmonary function features in a patient who has diffuse
parenchyma lung disease we generally will see a restrictive pattern of lung volumes
characterized by a relatively symmetric decrease in lung volumes, total lung capacity,
functional residual capacity, vital capacity, and residual volume. If we had to choose
one of them that is most important I would have to say it is the total lung capacity and
the low total lung capacity is really what defines the presence of a restrictive physiologic
pattern. We generally do not see airflow obstruction and that means that the FEV1/
forced vital capacity ratio is normal or actually may even be increased. However, if we
look at the FEV1 in isolation or if we look at the forced vital capacity in isolation they
may be down, but they are down in proportion to the other lung volumes. The key thing
is they may be decreased but the ratio between them the FEV1/forced vital capacity
ratio is normal. If we do see coexisting airflow obstruction based on a low FEV1 to
forced vital capacity ration then that may clue us in to a few disorders such as
histiocytosis X, which is the same as eosinophilic granuloma,
lymphangioleiomyomatosis a rare disorder that I will mention later, sarcoid, and cystic
fibrosis. All of those can have coexisting airflow obstruction. Typically the diffuse and
capacity is decreased in the diffuse parenchyma lung diseases. However, the diffuse and
capacity if it is increased we should think about alveolar hemorrhage because of red
cells in the alveolar spaces taking up carbon monoxide, or because of coexisting high
left atrial pressures because of increased blood volume within the lungs capable of
taking up carbon monoxide. That would be the case obviously with heart failure or
mitral valve disease.
Next I would like to go through a number of the specific disorders. I’ll try to focus on a
few of the interesting clinical features and treatment aspects of some of the diffuse
parenchyma lung diseases. I’ll start by talking about idiopathic pulmonary fibrosis or
IPF. If I gave this talk in England I would be talking about cryptogenic fibrosing
alveolitis. That is synonymous with idiopathic pulmonary fibrosis. Many people have
heard and think about the term Hamman-Rich syndrome, which was the term that was
coined in the 1940’s down at Hopkins for a disorder that was subsequently thought
perhaps to be idiopathic pulmonary fibrosis. If one goes back and looks at the original
cases of Hamman-Rich syndrome it turns out that these cases were actually quite a bit
different from what we think of as idiopathic pulmonary fibrosis now. The Hamman-
Rich cases were much more rapidly progressive and often lead to death within 6 months.
In contrast idiopathic pulmonary fibrosis is really a slowly progressive disease and one
that progresses with fibrosis that occurs over the course of years rather than months.
Although it can and certainly often does lead to respiratory failure and death as I said
the issue is that it progresses over years rather than months. The term DIP or
desquamative interstitial pneumonitis is in some ways similar to idiopathic pulmonary
fibrosis, but in some ways different. The pathology is slightly different in the sense that
there are cells within the alveolar spaces that actually represent macrophages. They are
not desquamative alveolar cells, but rather are intra-alveolar inflammatory cells. The
question that has come up is whether DIP represents a sub-type of idiopathic pulmonary
fibrosis with a fair amount of inflammation, or whether it represents a different disease
and that is really not clear. It has been however, suggested that maybe there is actually
more of an association with some small airways disease. Many of the patients who have
desquamated interstitial pneumonitis actually are smokers and they also often will have
an inflammatory process in the small airways and one of the questions that comes up is
this more of a smoking related disease as opposed to a non-smoking related disease such
as idiopathic pulmonary fibrosis. The treatment of IPF has really not improved much
over the past decade or even a couple of decades. We tend to just try to suppress the
inflammatory response with prednisone generally. There are many people who favor
using an immunosuppressive agent other than prednisone like cyclophosphamide has
been used. There has not been really good head to head studies comparing those and I
4.
Bronchoalveolar lavage (BAL) fluid shows lymphocytosis with
low
CD4/CD8 ratio
D. Eosinophilic granuloma (histiocytosis X)
1.
Atypical histiocytes (Langerhans' cells) in infiltrate; variety of cell
types in infiltrate with scattered eosinophils
2.
May have airflow obstruction; may have surprisingly normal lung
volumes for degree of interstitial disease seen on radiograph
3.
Chest X-ray and CT scan may show numerous small cysts and
nodules; eventual progression to fibrosis and honeycombing
4.
Presence of cysts explains possible clinical presentation with
spontaneous pneumothorax
5.
Very high association with smoking
6.
Quite variable natural history ranging from spontaneous resolution
to marked progression with honeycombing and endstage lung
7.
No clear response to any form of therapy, though
steroids/immunosuppressives often used
E.
Lymphangioleiomyomatosis
1.
Exclusively in women, almost all of childbearing age
2.
Atypical smooth muscle proliferation around lymphatics,
bronchioles, small pulmonary vessels
3.
Clinical presentation with any of the following: pleural effusion
(chylothorax), interstitial lung disease (with cysts, similar to
eosinophilic granuloma), spontaneous pneumothorax, hemoptysis
4.
Like eosinophilic granuloma, may have airflow obstruction, normal
lung volumes despite interstitial pattern on chest radiograph
5.
Treatment - alteration of hormonal milieu, e.g., progesterone,
oophorectomy
F.
Chronic eosinophilic pneumonia
1.
Often in patients with underlying asthma
2.
Term refers to eosinophils in the pulmonary, infiltrate, which is
interstitial and intra-alveolar
a.
Peripheral blood eosinophilia common but not present in all
patients
3.
Often subacute presentation with dyspnea, cough, fever, other
constitutional symptoms
4.
Typical peripheral distribution of infiltrates - photographic negative
of pulmonary, edema
5.
Often dramatic response to steroids - can be used for diagnostic trial
would say that if you’d look across the country as far as what pulmonologist do I would
say maybe 60% will start with prednisone and about 40% will start with an agent such
as cyclophosphamide. There really is no good data for head to head comparison.
Sarcoidosis is my favorite of the interstitial lung diseases. It also I think it is fair to say
the most common of the interstitial lung diseases. We still to this day do not what causes
sarcoidosis. The presumption is that sarcoid reflects a response to some agent, an
immunologic response to some agent, whether or not it is an exogenous agent or perhaps
even an indigenous agent isn’t really clear. It is also though that it may occur in any
genetically susceptible host, although that has also not been well worked out. At the
moment the National Institutes of Health has a multi-center study to try to sort out the
ideology of the sarcoid. We have medical center and one of the 10 centers and the hope
is by applying newer molecular biologic techniques we’ll be able to try to figure out
what the ideology of sarcoid is. However, we can state a few points about sarcoid in
terms of describing what happens. One of the interesting immunologic features is that
there seems to be a hyperactive T cell mediated immunologic response in the lungs that
seems to result in the formation of granulomas. If we look in the lungs to do a
bronchoalveolar lavage for example, we can find an increased number of lymphocytes in
the lungs and also a high helper to suppressor cell ratio, high CD4 to CD8 ratio. In
contrast, if we look in the peripheral blood for example, we find a depression of T cell
mediated responses as we think about things such as impaired delayed hypersensitivity
patients are often anergic on skin testing. However, unlike patients with HIV infection
this cutaneous anergy and sarcoid is not associated with an increased risk of
opportunistic infections. As I mentioned earlier radiographic patterns can be anything.
It can be reticulonodular, nodular, or alveolar. We often will see endobronchial
involvement. If we look with a bronchoscope we will see that there are often little bumps
sometimes called cobble stoning in the airway surface that is often responsible for a
significant problem with cough. In general angiotensin converting enzyme levels, which
had been proposed in the past to be useful in the diagnosis of follow-up of patients with
the disease. I would have to say, in general, most people felt that they are not useful.
There are a number of diseases that have been associated to high elevated levels
including other granulomas diseases and the correlation is not necessarily all that great
with activity of the disease. Corticosteroids remain the mainstay of therapy, but we
really do not have any good evidence that corticosteroids alter the overall natural history
of the disease even though they will acutely suppress many of the manifestations of the
disease. One might think because of the presumed pathogenic role of T cells
particularly T helper cells in this disease that cyclosporine might be useful, but actually
when it has been looked at the results have been quite disappointing so far. The other
agent that there is a lot of interest in is methotrexate used primarily as a steroid sparing
agent in this disease, but also potentially as a steroid alternative. There are some trials
that are going on right now, but I don’t think that we really have any definitive
information about the role of methotrexate versus steroids for sarcoid.
Another disorder in the lung that will often have some granulomas on pathology,
although they are not as well formed as the granulomas of sarcoid. This is
hypersensitivity pneumonitis. Examples are being farmer’s lung, air conditioner or
humidifier lung. For all of these basically the underlying pathogenesis is an
immunologic response to an inhaled organic antigen. In the case of farmer’s lung and
all of these what we are dealing with is a response to thermophilic Actinomyces, a mold
that can grow either in hay or can grow in a forced air system. The other common type
of organic antigen would be an antigen from animals such as antigens form birds as
could be seen in bird breeders. The pathology is poorly formed granulomas. The disease
can present either in an acute form or in a more chronic form. The acute form often
presents as fever, constitutional symptoms, shortness of breath, and pulmonary infiltrates
occurring 4 to 6 hours after exposure. The chronic form presents more as a diffuse
interstitial lung disease often in those patients where the underlying exposure is not
being recognized and they have repeated exposure. Interestingly enough if you look in
the lungs by doing a bronchoalveolar lavage and recover cells you’ll find that there is a
increased number of lymphocytes very similar to what we see in sarcoid, but they are
different lymphocytes. In sarcoid we have a high CD4 to CD8 ration where as in
hypersensitivity pneumonitis the converse is true where the CD4 to CD8 ratio is actually
low.
A few less common disorders and one is eosinophilic granuloma, which is also called
histiocytosis X. It turns out that the name of this is somewhat of a misnomer in the sense
that they really are not a huge number of eosinophils and we do not see well formed
granulomas in this disease. Rather what we see is an accumulation of a type of
histiocytic cell called the Langerhans’ cell, which is normally found in the dermis, but
there are also Langerhans’ cells that appear to be important in the antigen processing in
the lungs. These cells accumulate and they seem to proliferate in the lungs. It is not a
neoplastic disorder of these cells. What we see often is that airflow obstruction is
in setting of typical chest X-ray. Prolonged therapy (at least 6
months) usually necessary.
6.
Distinguish from acute eosinophilic pneumonia, an acute febrile
illness with hypoxemic respiratory, failure, diffuse pulmonary.
infiltrates, BAL eosinophilia, and a dramatic response to steroids
without recurrence after withdrawal
G. Bronchiolitis obliterans with organizing pneumonia (BOOP)
1.
Pathology - fibrous plugs in small airways; organizing inflammatory.
infiltrate in pulmonary, parenchyma
2.
Can be idiopathic (often called cryptogenic organizing
pneumonitis), related to infection, associated with connective tissue
disease
3.
Subacute illness with dyspnea, cough, constitutional symptoms
4.
Chest radiograph often with patchy or localized alveolar infiltrates;
can mimic bacterial pneumonia
5.
Responds well to steroids; generally treated for months
relatively common in eosinophilic granuloma largely because there are cysts that form.
I will show you this later. If one sees a combination of interstitial disease plus large
lung volumes, or associated obstructive disease then eosinophilic granuloma is one of
the disorders to consider. Chest x-rays and CT scans will often show nodular disease as
well as cysts. Because of the cysts patients may develop spontaneous pneumothorax if a
subpleural cyst ruptures. Interestingly enough there is an epidemiologic association of
this disorder with smoking that has never really been well worked out. We don’t
exactly know what it is, but the overwhelming majority of patients who have this disease
our smokers. The natural history is variable. In some cases the disease will resolve on
its own and in other cases the disease goes on to progressive respiratory insufficiency
and may require transplantation or it may lead to death. There is no proven treatment.
Often people will use things like corticosteroids, but in fact they have never been shown
to work. This is an example of a high resolution CT scan of a patient who has
eosinophilic granuloma and what you can see first of all is that there are some nodular
changes here. At the same time there are impressive cystic changes as well and these are
responsible to some extent for the airflow obstruction and also for the spontaneous
pneumothoraces that can develop. It is pretty is easy to see that if this thing adjacent to
the visceral pleural will rupture one will end with a spontaneous pneumothorax.
Another disease that in some respects looks a little bit similar, but also is different from
eosinophilic granuloma is the one that has the longest name of all the interstitial lung
diseases, which is, lymphangioleiomyomatosis often called LAM. It is an interesting
disorder and it occurs exclusively in women. Almost all of who are of childbearing age
and that certainly raises the issue if whether or not there may be a hormonal influence in
the production of the disease. The disease is characterized by atypical smooth muscle
cell proliferation. The smooth muscle cells will proliferate around lymphatics,
bronchioles, and small vessels. Involvement of each of these can lead to clinical
manifestations. For example, one can see pleural effusion as a result of lymphatic
blockage. You can see interstitial lung disease just as a result of the increased number of
smooth muscle cells. Pneumothorax can develop as a result of involvement of
bronchioles and airflow obstruction and cyst formation. Hemoptysis can occur as a
result of vessel involvement. Like eosinophilic granuloma airflow obstruction is
common, so one can see relatively normal lung volumes despite the presence of
interstitial lung disease on chest x-ray. The treatment of the disease is felt to be
hormonal manipulation and often what that may mean is progesterone therapy or
actually going ahead to oophorectomy. This is an example of a chest radiograph of
women with LAM. You can see that the lung volumes are actually very large here. The
diaphragms are down. If you could see the lateral you’d actually see that the
diaphragms are relatively flat. There is also sort of a hazy appearance over here. This is
not just breast shadow, but there is a very subtle interstitial pattern there as well.
Perhaps most dramatic though is the CT scan in someone like that. This is near the top
of the lungs in the patient with LAM and what you see in this case is a very severe
disease essentially all of the parenchyma is replaced with these cysts. It is really quite
striking. You really don’t see anything that looks like gas exchanging area of the lungs.
In fact, recognizing that this on a gross scale of a CT scan and this is more of what you
would expect to see microscopically histologically of what alveolar septi look like. It is
really quite striking.
Another disorder is one that I think is very important to recognize for clinicians because
it is really quite treatable and that is the disorder called chronic eosinophilic pneumonia.
This is a disorder that is characterized by eosinophils in a parenchymal infiltrate within
the lungs. The name eosinophilic pneumonia does not necessarily refer to peripheral
eosinophils. It refers to eosinophils in the infiltrate. It turns out that these patients often
will have peripheral eosinophilia, but they so not have to. The patients often will have
underlying asthma, but again they do not have to have that either. When they present
they present often over the course of weeks to even a month or two, so the presentation
is more subacute. They will often have respiratory symptoms and they may have
constitutional symptoms as well. By constitutional symptoms here I mean basically
they may have fever, fatigue, etc. One often makes attentive diagnosis or one thinks
through the diagnosis because of the finding of peripheral infiltrates, a so-called
photographic negative of pulmonary edema. Many people feel that this radiographic
pattern is typical enough so that one does not actually need to do a biopsy and one can
treat the patient with corticosteroids and use that as an empiric diagnostic and
therapeutic trial. The patients respond exquisitely to steroids so that often very dramatic
radiographic infiltrates will melt over the course of a few days. This is an example of a
patient who has chronic eosinophilic pneumonia and let me just point out toward the
periphery of the lung here, these whitish areas, this doesn’t represent scapula. It does not
represent pleural disease. It is actually parenchymal disease. On the other side as well
you can see that there is this extra white stuff here and some up in the upper lung zones
where as the more central areas are spared. Unlike what we think of with relatively
central pulmonary edema, often a butterfly pattern, this is the opposite of that and that is
III. Important diagnostic methods
A. High resolution CT scanning
1.
Width of cuts decreased from 10 mm to 1.0 or 1.5 ram, and special
algorithm used for spatial reconstruction
2.
Can detect subtle disease not apparent on chest X-ray
3.
Certain patterns suggestive of specific diagnoses
a.
Lymphangitic carcinoma - polygonal pattern
b.
Eosinophilic granuloma and lymphangioleiomyomatosis multiple
small cysts
c.
Sarcoidosis - bronchovascular pattern
d.
Idiopathic pulmonary fibrosis - heterogeneous pattern with
prominent subpleural disease and cyst formation
B. Bronchoalveolar lavage
1.
Most useful for recovery of organisms, e.g., Pneumocystis in AIDS
2.
Typical patterns in some diseases, but generally not specific enough
to replace biopsy
a.
Lavage lymphocytosis in sarcoidosis and hypersensitivity
pneumonitis; CD4/CD8 >2 in sarcoidosis and <1 in
hypersensitivity pneumonitis
b.
Profile variable in idiopathic pulmonary fibrosis - some with
increased PMNs, some with increased lymphocytes
3.
Histiocytosis X cells (with S-100 antigen) in eosinophilic granuloma
C. Thoracoscopic lung biopsy - has generally replaced open lung biopsy
because of better patient tolerance and shorter hospitalization
why this is called the photographic negative of pulmonary edema. We see this chronic
eosinophilic pneumonia and we also will see it in another slide after this. We may see it
in bronchiolitis obliterans with organizing pneumonia. In contrast to eosinophilic
pneumonia I do want to mention a disorder that is called acute eosinophilic pneumonia,
which does not develop over weeks to months, but rather often develops over days as an
acute febrile illness that is associated with hypoxemic respiratory failure. The patients
will have diffuse pulmonary infiltrates rather than the peripheral pulmonary infiltrates.
Like the patients with chronic eosinophilic pneumonia they will have lots of eosinophils
in the lung parenchyma. If you do a bronchoalveolar lavage on either of the disorders
you’ll find lots of eosinophils. These patients like the chronic eosinophilic pneumonia
patients will respond dramatically to steroids, but what is different and what is
interesting is that in the acute eosinophilic pneumonia patients once they are treated the
infiltrates melt and you taper them off steroids. They do not get a recurrence of their
disease. In contrast, patients with chronic eosinophilic pneumonia often need to be
treated over a number of months and if you withdrawal the steroids prematurely then the
disease will recrudesce.
The next disorder is bronchiolitis obliterans with organizing pneumonia or BOOP is
really characterized by the pathology, which reflects the title. The pathology will show
bronchiolitis obliterans, which in practice means that there are fibrous plugs in small
airways. The organizing pneumonia component means that one often sees in adjacent
alveolar spaces is what looks like a chronic or resolving inflammatory infiltrate often
with mononuclear cells. The ideology is there are a number of disorders that can be
associated with bronchiolitis obliterans with organizing pneumonia and therefore, rather
than being a specific disease that actually may be a syndrome that has several
underlying ideologies. The probably most common is idiopathic. It can also be
associated with infection as a post-infectious probably in the stage of resolution. It can
also be associated with some underlying connective tissue diseases. Like chronic
eosinophilic pneumonia the presentation is often subacute with respiratory and often
with constitutional symptoms. The chest x-ray shows patchy or localized infiltrates and
the treatment is generally with corticosteroids. These patchy or localized infiltrates may
be very non-specific. They may look just like pneumonia and sometimes may have a
peripheral distribution mimicking chronic eosinophilic pneumonia. This is an example
of a patient with BOOP. You should ignore the fact that there is an enlarged heart here.
This patient also had an underlying cardiomyopathy that was really not related. What
the patient did have were these infiltrates. Here is one that is actually very much an
alveolar filling pattern on the left side as well as another patchy infiltrate on the right.
This patient was found by biopsy to have BOOP and was treated with steroids and the
infiltrates melted.
Diagnostic methods and some of the newer diagnostic methods that are used in patients
that have diffuse parenchymal lung disease. First of all, high resolution CT scan is now
very important in the diagnostic evaluation of these patients for 3 reasons. First of all,
there are some patients where we can detect very subtle disease where the chest x-ray is
actually normal, but the CT scan will show subtle abnormalities that just were not
detected. Secondly, there are some disease specific patterns and I’ll show you some of
these things such as lymphangitic spread of carcinoma, eosinophilic granuloma, and
lymphangioleiomyomatosis. All of those have relatively typical patterns on CT scans
that can suggest the diagnosis. Finally there is interest in whether or not the pattern of
abnormality on CT scan reflects the activity of the disease with a ground-glass pattern
suggesting more active and more inflammatory disease. This is an example of a CT
scan in a patient who was short of breath, had restrictive disease on pulmonary function
tests, and had a normal chest x-ray. The high resolution CT scan shows a patchy pattern
of a sort of ground-glass increase in density and in between the areas of increased
density are relatively normal areas that look sort of hypodense here. It turns out that the
blacker areas are not the abnormal areas. It is not like these are cysts or areas of
emphysema. If you could see the original you’d see that there are actually lung
markings going through these areas, rather it is the ground-glass or somewhat whitish
areas that are the abnormal areas. This patient on biopsy turned out to have a
hypersensitivity pneumonitis and actually this particular pattern is often seen in patients
who have a hypersensitivity pneumonitis. In contrast, this is sort of a linear pattern and
actually is affecting a lot of interlobular septi and this is a pattern that we commonly
will see in the spread of tumor throughout the lungs. Sometimes it is described as a
polygonal pattern and may have geometric shapes. This is a high resolution CT scan of
the patient with idiopathic pulmonary fibrosis, which often has a pattern of distribution
of a fair amount of fibrosis out toward the periphery of the lungs. You can see several
areas here often patchy and are often associated with some cyst formation. This is a
pattern that is quite typical.
Another technique that is used and is relatively new is one called bronchoalveolar
lavage. It is used primarily for recovery of organisms certainly in patients who have
References
1.
DePaso WJ, Winterbauer RH. Interstitial lung disease. Dis Mon 37:61-133,
1991. Excellent recent review of the interstitial lung diseases.
2.
Silver RM, Miller KS, Kinsella MB, Smith EA, Schabel SI. Evaluation and
management of scleroderma lung disease using bronchoalveolar lavage. Am
J Med 88:470-476, 1990. 49% of patients with scleroderma had BAL
evidence of an active alveolitis; these patients appeared to have some
improvement following
treatment with cyclophosphamide and prednisone.
3.
Panos RJ, Mortenson RL, Niccoli SA, King TE Jr. Clinical deterioration in
patients with idiopathic pulmonary fibrosis. Am J Med 88:396-404, 1990.
Besides progression of disease, patients may have disease-related
complications, e.g., lung cancer (10%), pneumothorax, corticosteroid side
effects, including immunosuppression.
4.
Lower EE, Baughman RP. Prolonged use of methotrexate for sarcoidosis.
Arch Intern Med 155:846-851, 1995. The authors present their generally
positive (but uncontrolled) experience with methotrexate in sarcoidosis.
5.
Muller NL, Miller RR. Computed tomography of chronic diffuse infiltrative
lung disease. Am Rev Respir Dis 142:1206-1215, 1440-1448, 1990.
Excellent review of CT scanning, including high resolution CT scanning, in
the evaluation of diffuse infiltrative lung disease.
6.
Kalassian KG, Doyle R, Kao P, Ruoss S, Raffin TA.
Lymphangioleiomyomatosis: new insights. Am J Respir Crit Care Med
155:1183-1186, 1997. A recent short review of LAM.
7.
Muller NL, Ostrow DN. High-resolution computed tomography of chronic
interstitial lung disease. Clin Chest Med 12:97-114, 1991. Excellent
overview of high-resolution CT scanning in interstitial lung disease.
HIV infection, but in addition it can be used for cell characterization more actually on a
research basis then for differential diagnosis of patients with interstitial lung disease.
However, as I mentioned earlier one does find an increased number of lymphocytes in
sarcoid and in hypersensitivity pneumonitis, but the CD4/CD8 ratios are different. The
CD4 to CD8 is high in sarcoid and it is actually low in hypersensitivity pneumonitis.
Idiopathic pulmonary fibrosis will have high numbers of either polys or lymphocytes, so
that is not particularly useful diagnostically. In histiocytosis X or eosinophilic
granuloma one can actually find certain changes in the cells. One can detect what’s
called the S-100 antigen, which identifies those Langerhans’ cells and one can
potentially even make a diagnosis of EG just on the basis of lavage. Finally,
thoracoscopic lung biopsy is where the surgeon will go in with what is the equivalent of
the chest version of laparoscopy where a scope is used to get into the pleural space and
get lung biopsy specimens. That now has really essentially in many cases replaced open
lung biopsy for obtaining a diagnosis in some of these patients, so when we are thinking
of getting diagnostic tissue are main options these days are either transbronchial biopsy
or a thoracoscopic lung biopsy.
