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NLS-diagnostics of diffuse infiltrative lung diseases
V.I.Nesterova, T.G.Kuznetsova, N.L.Ogluzdina

Among different kinds of lungs disorders special attention has been paid over the last years to diffuse infiltrative lung diseases (DILD), which is largely accounted or by some problems in their timely diagnostics and treatments.
Most diffuse lung diseases involved in the pathological process both the interstitial tissue and the respiratory tract and alveola. In this connection this type of pathological processes should be defined rather diffuse infiltrative than as interstitial diseases. Despite of the polymorphism of clinicomorphological manifestation of DILD, most of them star off with productive alveolitis (in contrast to the exudative alveolitis in the case of pneumonia) with fairly stereotyped changes in the lung interstice in the form of inflammatory infiltration with different degrees of intensity. Subsequently fibrosis develops that can have differen rates of progression. A "cellular lung" pattern is the final phase of development. It should be noted, that some infection diseases of certain etiology (like tuberculosis, histoplasmosia, etc.) and particular malignant tumors (lymphogenous, carcinomatosis, brioncholoalveolar cancer) do not directly belong to interstitial lund diseases but are similar to them in terms of manifestation.

The clinical evaluation of patients which are suspected DILD is a complex problem. Nonspecific symptoms and in some cases sing detected during chest examination may be characteristic of a multitude acute or chronic diseases that involve interstitial tissue, respiratory tract or alveola. DILD are represented by extremely heterogeneous group of diseases. The DLIDs have been describe in over than a hundred possible versions , however in clinical practice only about 10 or 15 condition are the 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-infection) are likely to have a great number of infectious and non-infectious varieties, which X-ray evaluation is forum to be difficult.

Unfortunately, the capabilities of conventional peonthenography for patient with a suspected DILD appear to be limited for the sensitivity and specificity of the method prove to be insufficient. The data on 458 patients with a histological 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 over 20% of the patients with emphysema shown on X-ray shot. Radiography may equally show false positive results of the investigation. We have discovered that 10-20% of the patients with the x-ray-confirmed sings of DILD no changes were detected during the lung biopsy.

The computer nonlinear diagnostics (NLS) is one of the promising methods of diagnosing lung disease of today. NLS appreciably improves the communication of the fine morphological elements in the lungs tissue and opens up new opportunity for recognizing interstitial discases of the broncholveolar system. NLS has a high sensitivity in detecting fine interstinal lesions of the parenchyma and small nodules.

The result of investigations prove that NLS has a better sensitivity in detecting both acute and chronic diffuse lung diseases. The sensitivity of NLS diagnosis in detecting lung disease make 85% as compared to 79% in chest radiography.
The accumulated experience too, give 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 by sensitivity.
It should be noted that the high sensitivity of the NLS-method is achieved without sacrificing the specific 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 (87088%) and specificity (83-89%) of NLS were demonstrated in bronchiectasia diagnostic.

Although, NLS is a more sensitive method as compared to the chest radiography, its sensitivity in lung diseases diagnostic 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 changes in the lungs.
Despite the high value of NLS sensitivity and specificity, for 4% of the patients with biopsy-detected lung disease the result were interpreted as being normal. On other hand, the NLS was proven to high-accuracy technique for precluding acute lung disease 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. Beside, the fact that no changes were detected during NLS lung examination allows to assume 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 (10 mm collimation) and NLS we found that NLS had higher sensitivity in recognizing pathology 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 acute or chronic diffuse lung disease.
Even with certain clinical sings in evidence the diagnostic accuracy of classic radiography in patients affected by DILD apperes to be limited. The reason is both superposition of the image in the radiograph and low contrast of minute lung structure. NLS is fee of these aspects, which is why it is reputed to be a more efficiency method for recognizing lesions of lung tissue as compared to both radiographic survey and conventional computer tomography.

Beside 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 patient affected by DILD. In certain cases NLS can be used not only to define the presence of a pathological process or the extent to which it has spread, but also to collect information about the reversibility of changes (in acute or active phase) as compered 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 the patients.
The conventional methods for evaluating disease activity, such as transbronchial lung biopsy (TBLB), bronchoalveolar lavage (BAL), chest radiography, galliumlung scanning and functional lung tests are insufficient reliable I 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 sings 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 this prognostic value NLS is advancing to the foreground leaving behind functional lung tests, BAL and even OLB, because it allows to assess a lesion of actually the whole lung paranchymes 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 common interstitial lung disease 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 researches considered the NLS potential in defining the procsess activity in patients affected by sarciodosis. The main activity indicator is the presence of small nodules and to 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 potential of NLS is assessing the process activity have not been studied well enough.

Among differential indications in favor of NLS application, the use of this method in lung biopsy is porbable the most important one. Biopsy is very essential diagnostics technique which allows to define the nosology of lung disease, 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.

At the same time OLB made a specific diagnosis of DILD in 92% of cases. In DILD-affected patients TBLB proved to be most informative for patients having sarcoidosis or lymphogenous carcinomatosis, because this lesions have largely peribronchical tissue involved and are therefore most accessible to TBLB. Diagnostically 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 the lung may contine both actibe manifestations of te disease and fibriotic changes of long standing. For any accurate diagnostis and assessment af the clinical progres of the disease the rifht choice of a biopsy smaple is very important. During biopsy NLS helps to collect moere 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 ( TBLS, BAL, OLB) for making a histological diagnosis.
Conclusion. Radiography still remines the most/accessiable method for diagnosing DILD yet its informational content apperes to be not sufficient.

Making correct diagnosis necessitates a combination of laboratory, functional and radiological investigations as well as some invasive methods, cach of them having it sown substantial limitations.

NLS-diagnostics is the method that greatly improves identification of diffuse infiltrative lung disease and as such it should become a part and parcel of an integrate investigation

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