Metatron HunterNLS-Diagnosis of Diffuse Infiltrative Lung Diseases
V.I. Nesterova,
T.G. Kuznetsova,
N.L. Ogluzdina
Among different kinds of lung disorders special attention has been paid over the last
years to diffuse infiltrative lung diseases (DILD), which is largely accounted for by some
problems in their timely diagnosis and treatment.
Most diffuse lung diseases involve in the pathological process both the interstitial tissue
and the respiratory track and alveoli. In this connection this type of pathological
processes should be defined rather as diffuse infiltrative than as interstitial diseases.
Despite of the polymorphism of clinico-morpholitis (in contrast to the exudative alveolitis
in the case of a pneumonia) with fairly stereotyped changes in the lung interstice in the
form of inflammatory infiltration with different degrees of intensity. Subsequently a
fibrosis develops that can have different rates of progression. A ‘cellular lung’ pattern is
the final phase of the development. It should be noted, that some infectious diseases of
certain etiology (like tuberculosis, histoplasmosis, etc.) and particular malignant tumors
(lymphogenous carcinomatosis, bronchioloalveolar cancer) do not directly belong to
interstitial lung diseases but are similar to them in terms of manifestation.
The clinical evaluation of patients with a suspected DILD is a complex problem.
Nonspecific symptoms and in some cases signs detected during chest examination may
be characteristic of a multitude of acute or chronic lung diseases that involve the
interstitial tissue, respiratory tract or alveoli. DILD are represented by an extremely
heterogeneous group of diseases. The DILDs have been described in over a hundred
possible versions, however in clinical practice only about 10 or 15 conditions are most
common and it should be noted that sarcoidosis and various cases of lung fibrosis occur
in clinical practice in 35-50% of all DILDs. Besides, acute diffuse lung processes in
patients with reduced immunity (also in combination with HIV-infections) are likely to
have a great number of infectious and non-infectious varieties, which X-ray evaluation is
found to be difficult.
Unfortunately, the capabilities of conventional roentgenography for patients with a
suspected DILD appear to be limited for the sensitivity and specificity of the method
prove to be inefficient. The data on 458 patients with a histologically confirmed DILD
were studied. The chest radiographs for 10% of the cases turned out to be normal.
Among 86 patients affected by DILD no pathological change was detected in 50% of the
patients with histologically proven bronchiectasia and in over 20% of the patients with
emphysema shown on X-ray shots. Radiography may equally show false positive results
of the investigation. We have discovered that in 10-20% of the patients with the x-ray
confirmed signs of DILD no changes were detected during the lung biopsy.
The computer nonlinear diagnostixs (NLS) is one of the promising methods of
diagnosing lung diseases of today. NLS appreciably improves the communication of the
26fine morphological elements in the lung tissue and opens up new opportunities for
recognizing interstitial diseases of the broncho-alveolar system. NLS has a high
sensitivity in detecting the interstitial lesions of the parenchyma and small nodules.
The results of the investigations prove that NLS has a better sensitivity in detecting both
acute and chronic diffuse lung diseases. The sensitivity of the NLS diagnosis in detecting
lung diseases makes 85% as compared to 70% in chest radiography.
The accumulated experience too, gives additional grounds to assert that NLS is a highly
efficient method for diagnosing a wide range of various diffuse lung diseases (DILD
included) and excels the ‘classic’ chest radiography in sensitivity.
It should be noted that the high sensitivity of the NLS-method is achieved without
sacrificing the specificity and diagnostic accuracy of the method. In patients affected by DILD
the NLS specificity amounted to 86% as opposed to 76% in radiography. In
particular, the high sensitivity (86-88%) and specificity (83-89%) of NLS were
demonstrated in bronchicetasia diagnosis.
Although NLS is a more sensitive method as compared to chest radiography, its
sensitivity in lung disease diagnosis is not absolute and the fact that no radiological
changes were detected by NLS may lead to precluding lung disease in patients who
actually suffer from DILD. 100 patients were examined by means of the NLS with 86 of them
affected by DILD and 14 having no pathological change in the lungs.
Despite a high value of NLS sensitivity and specificity, for 4% of the patients with biopsydetected lung diseases the results were interpreted as being normal. On the other hand,
the NLS was proven to be a high-accuracy technique for precluding acute lung diseases
in patients with immunodeficiency. Some examination data were studied for patients with
a bone marrow transplant and clinical symptoms of fever of obscure genesis. The authors
demonstrated high reliability of the NLS in determining fungal infection in 20 of 24 cases.
Besides, the fact that no changes were detected during NLS lung examination prompts the
assumption that the fever was caused by bacterial or fungal infection of extra
pulmonary genesis.
It is also a proven fact that the sensitivity with NLS is higher than with standard computer
tomography. We examined 150 patients. Using conventional CT (10mm collimation)
and NLS we found that NLS had a higher sensitivity in recognizing pathological changes in the
lung tissue.
Due to its high sensitivity, NLS should be used to define lung diseases in patients with a
normal or obscure aspect of disease who have a pulmonary disturbance or symptoms that
suggest an acute or chronic diffuse lung disease.
Even with certain clinical signs in evidence the diagnostic accuracy of classic
radiography in patients affected by DILD appears to be limited. The reason is both
superposition of the image in the radiograph and low contrast of minute lung structures.
27NLS is free of these aspects, which is why it is reputed to be a more efficient method for
recognizing diffuse lesions of lung tissue as compared to both radiographic survey and
conventional computer tomography.
Besides, having a higher sensitivity, specificity and diagnostic accuracy, the NLS method
can become a determining factor in evaluating the activity of a pathological process in
patients affected by DILD. In certain cases NLS can be used not only to define the
presence of absence of a pathological process or the extent to which it has spread, but
also to collect information about the reversibility of changes (in an acute or active phase)
as compared to irreversible (fibriotic) changes in the lung tissue. Moreover, since NLS
can accurately identify the imponderable activity of a pathological process in the lungs, it
can be employed to evaluate the efficiency of the treatment given to patients.
The conventional methods for evaluating disease activity, such as trans-bronchial lung
biopsy (TBLB), broncho-alveolar lavage (BAL), chest radiography, gallium lung
scanning and functional lung tests are insufficiently reliable in evaluating the activity and
in terms of prognostication. So the open lung biopsy (OLB) is still the choice method for
both diagnosing and evaluating the process activity. We were able to prove, that signs
detected in patients by means of NLS can provide some valuable information and be
significantly important in defining the activity of a pathological process.
In terms of its prognostic value NLS is now advancing to the foreground leaving behind some
functional lung tests BAL and even OLB, because it enables lesion assessment over the
whole lung parenchyma as compared to a separate biopsy sample. Moreover, NLS
can become an accurate noninvasive method for evaluating the efficiency of the
administered treatment.
Sarcoidosis is one of the most interstitial lung diseases of unknown etiology. In typical
cases granulomas are formed in fine lymph vessels or beside them, afterwards the
granulomas self organize which causes lung tissue fibrosis.
A number of researchers considered the NLS potentials in defining the process activity in
patients affected by sarcoidosis. The main activity indicator is the presence of small
nodules and to a lesser degree their distribution and occurrence in the lung tissue.
Unfortunately, despite the difference between reversible and irreversible changes
detected by NLS for patients having sarcoidosis, the potentials of NLS in assessing the
process activity have not been studied well enough.
Among different indications in favor of NLS application, the use of this method in lung biopsy
is probably the most important one. Biopsy is a very essential diagnosis technique which
enables to define the nosology of a lung diseases, its activity level and phase. The diagnostic
value of biopsy to a certain degree depends on its method and the type of
DILD. The authors proved that TBLB was diagnostically informative for only 20
patients of 53 (38%) who had DILD in evidence; in 33 such patients (62%) TBLB
displayed normal lung tissue or nonspecific changes.
28At the same time OLB made a specific diagnosis of DILD in 92% of cases. In DILDaffected patients TBLB proved to be the most informative for patients having sarcoidosis
or lymphogenous carcinomatosis, because these lesions have largely peribronchial tissue
involved and are therefore most accessible to TBLB. Diagnosticly OLB appears to be
more accurate, but it also has certain complexities because lung tissue is sampled from a
small sector of the lung which might not reflect the changes occurring in the rest of the
lung tissue. Many diffuse diseases affect lung tissue irregularly so the pathologically
altered parts of lung parenchyma may be located among normal lung tissue. Besides, the
same lung may contain both active manifestations of the disease and fibrotic changes of
long standing. For an accurate diagnosis and assessment of the clinical progress of the
disease the right choice of a biopsy sample is very important. During biopsy NLS helps
to collect more accurate data indicating active areas of a pathological process. By using
NLS, the areas affected by lung fibrosis in its final phase, with ‘honeycomb’ lung formed,
could be skipped during biopsy sampling. In addition, NLS may prove to be vitally
important for choosing the most effective technique (TBLB, BAL or OLB) for making a
histological diagnosis.
Conclusion.
Radiography still remains the most accessible method for diagnosing DILD yet its
informational content appears to be inadequate.
Making a correct diagnosis necessitates a combination of laboratory, functional and
radiological investigations as well as some invasive methods, each of them having its
own substantial limitations.
NLS-diagnosis is a method that greatly improves identification of diffuse infiltrative lung
diseases and as such it should become a part and parcel of an integrated investigation