NLS-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 biopsy-

detected 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 DILD-

affected 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.