Idiopathic Fibrosing Alveolitis - Clinical Guidelines, General Information

2024 Author: Josephine Shorter | [email protected]. Last modified: 2024-01-07 17:49

Idiopathic fibrosing alveolitis: etiology, pathogenesis, treatment

Idiopathic fibrosing alveolitis (ELISA) is a disease that remains one of the least studied, among other pathologies of the interstitium of the lungs. With this type of alveolitis, inflammation of the pulmonary interstitium with its fibrosis occurs. The airways and lung parenchyma are also affected. This negatively affects the state of the respiratory system, leads to their restrictive changes, disruption of gas exchange and respiratory failure, which becomes the cause of death.

Idiopathic fibrosing alveolitis is also called idiopathic pulmonary fibrosis. This terminology is used mainly by English specialists (idiopathic pulmonary fibrosis), as well as German pulmonologists (idiopa-thische Lungenfibrose). In the UK, ELISA is called "cryptogenic fibrosing alveolitis" (cryptogenic fibrosing alveolitis).

The terms "cryptogenic" and "idiopathic" have some differences, but they are now used interchangeably. Both of these words mean that the cause of the disease remains unclear.

Content:

• Epidemiology and risk factors
• Structural changes in the lungs
• Symptoms of idiopathic fibrosing alveolitis
• Diagnosis of idiopathic fibrosing alveolitis
• Treatment of idiopathic fibrosing alveolitis
• Treatment of complications
• Forecast

Epidemiology and risk factors

The statistics on the prevalence of the disease are very contradictory. It is assumed that such discrepancies are due to the consideration of patients not only with idiopathic fibrosing alveolitis, but also with other idiopathic interstitial pneumonia (IIP).

Out of 100,000 men, 20 people face pathology, and out of 100,000 women - 13 people. In a year, 11 people fall ill for every 100,000 men, and 7 people for every 100,000 women.

Although the causes of idiopathic alveolitis are currently unknown, scientists are still trying to find out the true nature of the origin of the disease. There is an assumption that the pathology has a genetic basis, when a person has a hereditary predisposition to the formation of fibrous tissues in the lungs. This happens in response to any damage to the cells of the respiratory system. Scientists confirm this hypothesis by a family history, when the disease is traced in blood relatives. Also in favor of the genetic basis of the disease indicates that pulmonary fibrosis often manifests itself in patients with hereditary pathologies, for example, with Gaucher disease.

Structural changes in the lungs

The main characteristics of the morphological picture of idiopathic fibrosing alveolitis are:

• The presence of dense fibrosis of the pulmonary parenchyma.
• Morphological changes are distributed according to the patchy heterogeneous type. Such spotting is due to the fact that areas of healthy and damaged tissues alternate in the lungs. The changes can be fibrous, cystic and interstitial inflammation.
• The upper part of the acinus is early involved in the inflammatory process.

In general, the histology of lung tissue in idiopathic fibrosing alveolitis resembles a similar picture as in interstitial pneumonia.

Symptoms of idiopathic fibrosing alveolitis

Most often, fibrosing idiopathic alveolitis is diagnosed in patients over 50 years of age. Men get sick more often than women. The approximate ratio is 1.7: 1.

Patients report shortness of breath, which gets worse. The patient is not able to take a deep breath (inspiratory shortness of breath), he is pursued by a dry cough without sputum production. Dyspnea occurs in all patients with idiopathic fibrosing alveolitis.

The stronger the shortness of breath, the more severe the course of the disease. Having appeared once, it no longer passes, but only progresses. Moreover, its occurrence does not depend on the time of day, on the ambient temperature and other factors. Patient's inspiratory phases are shortened as well as expiratory phases. Therefore, the breathing of such patients is rapid. Each of them has hyperventilation syndrome.

If a person wants to take a deep breath, then this leads to a cough. However, cough does not develop in all patients, therefore, in the diagnostic sense, it is not of interest. While people with chronic obstructive pulmonary disease, which is often confused with ELISA, cough will always be present. As the disease progresses, shortness of breath leads to the fact that the person becomes disabled. He loses the ability to pronounce a long phrase, cannot walk and take care of himself on his own.

The pathology manifesto is subtle. Some patients note that fibrosing alveolitis began to develop in them like ARVI. Therefore, some scientists suggest that the disease may be viral in nature. Since pathology develops slowly, a person manages to adapt to his shortness of breath. Unbeknownst to themselves, people reduce their activity and move to a more passive life.

A productive cough, that is, a cough accompanied by sputum production, develops in no more than 20% of patients. Pus may be present in the mucus, especially in those patients who suffer from severe idiopathic fibrosing alveolitis. This symptom is dangerous, as it indicates the addition of a bacterial infection.

An increase in body temperature and the appearance of blood in sputum are not typical for this disease. While listening to the lungs, the doctor auscultates crepitations that occur at the end of inspiration. If blood appears in the sputum, the patient should be referred for examination for lung cancer. This disease is diagnosed in patients with ELISA 4-12 times more often than in healthy people, even those who smoke.

Other ELISA symptoms include:

• Joint pain.
• Muscle pain.
• Deformations of the nail phalanges, which begin to resemble drumsticks. This symptom occurs in 70% of patients.

Crepitations at the end of inhalation become more intense and at the beginning they will be more tender. Experts compare the final crepitus with the crackling of cellophane or with the sound that is emitted when the zipper is opened.

If, at an early stage of the development of the disease, crepitus is heard mainly in the posterior basal regions, then as it progresses, squeaks will be heard over the entire surface of the lungs. Not at the end of the inhalation, but throughout its entire length. When the disease has just begun to develop, crepitus may be absent when the trunk is tilted forward.

Dry wheezing is heard in no more than 10% of patients. Most often, their cause is associated bronchitis. Further development of the disease leads to the onset of symptoms of respiratory failure, the development of cor pulmonale. The color of the skin acquires an ash-cyanotic color, 2 tone above the pulmonary artery increases, the heartbeat increases, the cervical veins swell, the limbs swell. The final stage of the disease leads to pronounced weight loss in a person, up to the development of cachexia.

Diagnosis of idiopathic fibrosing alveolitis

Methods for diagnosing idiopathic fibrosing alveolitis have been revised at this point in time. Although such a research technique as an open lung biopsy gives the most reliable result and is considered the "gold standard" of diagnosis, it is not always practiced.

This is due to the significant disadvantages of open lung biopsy, among which: the procedure is invasive, it is expensive, after its implementation, treatment will need to be postponed until the patient recovers. In addition, the biopsy will fail multiple times. For a certain part of patients, it is completely impossible to fulfill it, since the state of human health does not allow it.

The basic diagnostic criteria that have been developed for the detection of idiopathic fibrosing alveolitis are:

• Other pathologies of the interstitium of the lungs are excluded. This refers to diseases that could be triggered by taking medications, inhaling harmful substances, systemic damage to the connective tissue.
• The function of external respiration is reduced, gas exchange in the lungs is impaired.
• During the CT scan, bilateral reticular changes are found in the lungs, in their basal regions.
• Other diseases are not confirmed after performing transbronchial biopsy or bronchoalveolar lavage.

Additional diagnostic criteria include:

• The patient is over 50 years old.
• Shortness of breath occurs imperceptibly for the patient, increases with physical exertion.
• The disease has a long course (from 3 months or more).
• Crepitation is heard in the basal parts of the lungs.

In order for the doctor to be able to make a diagnosis, it is necessary to find confirmation of 4 main criteria and 3 additional ones. Evaluation of clinical criteria allows ELISA to be determined with a high degree of probability, up to 97% (data provided by Raghu et al), but the sensitivity of the criteria itself is equal to 62%. Therefore, about a third of patients still need a lung biopsy.

High-precision computed tomography improves the quality of lung examination and facilitates the diagnosis of ELISA, as well as other similar pathologies. Its research value is equivalent to 90%. Many experts insist on completely abandoning biopsy, provided that high-precision tomography has revealed changes characteristic of idiopathic alveolitis. In this case, we are talking about the "cellular" lung (when the lesion area is 25%), as well as histological confirmation of the presence of fibrosis.

Laboratory diagnostics has no global significance in terms of pathology detection.

The main characteristics of the analyzes obtained:

• Moderate increase in ESR (diagnosed in 90% of patients). If the ESR increases significantly, then this may indicate a cancerous tumor, or an acute infection.
• Increased cryoglobulins and immunoglobulins (in 30-40% of patients).
• Increased antinuclear and rheumatoid factors, but without revealing systemic pathology (in 20-30% of patients).
• Increased serum levels of total lactate dehydrogenase, which is due to increased activity of alveolar macrophages and type 2 alveocytes.
• Increased hematocrit and erythrocyte levels.
• An increase in the level of leukocytes. This indicator may be a sign of infection, or a sign of taking glucocorticosteroids.

Since fibrosing alveolitis leads to disturbances in the functioning of the lungs, it is important to assess their volume, that is, their vital capacity, total capacity, residual volume and functional residual capacity. When performing the test, the Tiffno coefficient will be within the normal range, or even increase. Analysis of the pressure-volume curve will show its shift to the right and downward. This indicates a decrease in lung compliance and a decrease in their volume.

The described test is highly sensitive, therefore it can be used for early diagnosis of pathology, when other studies do not yet reveal any changes. For example, a resting blood gas test will not reveal any abnormalities. A decrease in the partial tension of arterial blood oxygen is observed only with physical exertion.

In the future, hypoxemia will be present even at rest and be accompanied by hypocapnia. Hypercapnia develops only at the end of the disease.

When carrying out radiography, it is most often possible to visualize changes of the reticular or reticulonodular type. They will be found in both lungs, at the bottom.

Reticular tissue with fibrosing alveolitis becomes coarse, cords, cystic enlightenments with a diameter of 0.5-2 cm are formed in it. They form the picture of a "cellular lung". When the disease reaches the terminal stage, it is possible to visualize tracheal deviation to the right and tracheomegaly. At the same time, specialists should take into account that in 16% of patients, the X-ray picture can remain within normal limits.

If the patient's pleura is involved in the pathological process, intrathoracic adenopathy develops and parenchymal compaction becomes noticeable, then this may indicate a complication of ELISA by a cancerous tumor, or another lung disease. If the patient simultaneously develops alveolitis and emphysema, then the lung volume may remain within normal limits, or even be increased. Another diagnostic sign of a combination of these two diseases is a weakening of the vascular pattern in the upper part of the lungs.

While performing high-resolution computed tomography, doctors detect the following symptoms:

• Irregular linear shadows.
• Cystic enlightenment.
• Focal foci of a decrease in the transparency of the pulmonary fields as "ground glass". The area of lung injury is 30%, but no more.
• Thickening of the walls of the bronchi and their irregularity.
• Disorganization of the pulmonary parenchyma, traction bronchiectasis. The basal and subpleural parts of the lungs are more affected.

If the CT scan is assessed by a specialist, then the diagnosis will be 90% correct.

This study makes it possible to distinguish idiopathic fibrosing alveolitis from other diseases that have a similar picture, including:

• Chronic hypersensitive pneumonitis. With this disease, the patient has no "cellular" changes in the lungs, centrilobular nodules are visible, and the inflammation itself is concentrated in the upper and middle parts of the lungs.
• Asbestosis. In this case, the patient develops pleural plaques and parenchymal fibrosis ribbons.
• Desquamative interstitial pneumonia. Frosted glass shades will be extended.

Based on the data of computed tomography, a prognosis for the patient can be made. It will be better for patients with ground glass syndrome and worse for patients with reticular changes. An intermediate prognosis is indicated for patients with mixed signs.

This is due to the fact that patients with ground glass syndrome respond better to glucocorticosteroid therapy, which is reflected by the characteristic features of HRCT. Now doctors are more guided by computed tomography data when making a forecast than other methods (lavage of the bronchi and alveoli, pulmonary tests, lung biopsy). It is computed tomography that makes it possible to assess the degree of involvement of the lung parenchyma in the pathological process. While a biopsy makes it possible to examine only a certain area of organs.

Bronchoalveolar lavage should not be excluded from diagnostic practice, since it makes it possible to determine the prognosis of pathology, its course and the presence of inflammation. In lavage with ELISA, an increased number of eosinophils and neutrophils is found. At the same time, this symptom is typical for other diseases of the lung tissue, so its importance should not be overestimated.

A high level of eosinophils in lavage worsens the prognosis of idiopathic fibrosing alveolitis. The fact is that such patients most often respond poorly to treatment with corticosteroid drugs. Their use can reduce the level of neutrophils, but the number of eosinophils remains as before.

If high concentrations of lymphocytes are found in the lavage fluid, this may indicate a favorable prognosis. Since their increase often occurs with an adequate response of the body to treatment with corticosteroids.

Transbronchial biopsy allows you to obtain only a small area of tissue (no more than 5 mm). Therefore, the informative value of the study is reduced. Since this method is relatively safe for the patient, it is practiced in the early stages of the development of the disease. Biopsy allows to exclude pathologies such as sarcoidosis, hypersensitive pneumonitis, cancers, infections, eosinophilic pneumonia, histocytosis, alveolar proteinosis.

As mentioned, an open biopsy is considered a classic ELISA diagnostic method, it allows you to accurately diagnose, but it is impossible to predict the development of pathologists and its response to the forthcoming treatment using this method. Thoracoscopic biopsy can replace an open biopsy.

This study involves the collection of a similar amount of tissue, but the duration of the drainage of the pleural cavity is not as long. This reduces the time the patient spends in the hospital. Complications from a thoracoscopic procedure are less common. As studies show, open biopsy is inappropriate to prescribe to all patients without exception. It is really required only for 11-12% of patients, but no more.

In the international classification of diseases, revision 10, ELISA is defined as "J 84.9 - Interstitial pulmonary disease, unspecified".

The diagnosis can be formulated as follows:

• ELISA, early stage, respiratory failure 1 degree.
• ELISA at the stage of "cellular lung", respiratory failure of the 3rd degree, chronic cor pulmonale.

Treatment of idiopathic fibrosing alveolitis

Effective methods of ELISA treatment have not yet been developed. Moreover, it is difficult to give a conclusion about the effectiveness of the results of therapy, since data on the natural course of the disease are minimal.

Treatment is based on the use of drugs that reduce the inflammatory response. Corticosteroids and cytostatics are used, which have an effect on human immunity and help reduce inflammation. This therapy is explained by the assumption that idiopathic fibrosing alveolitis develops against a background of chronic inflammation, which entails fibrosis. If this reaction is suppressed, then the formation of fibrotic changes can be prevented.

There are three possible directions of therapy:

• Treatment with glucocorticosteroids only.
• Treatment with glucocorticosteroids with azathioprine.
• Treatment with glucocorticosteroids with cyclophosphamide.

The international consensus, held in 2000, advises to use the last two regimens in the treatment, although there is no evidence in favor of their effectiveness in comparison with glucocorticosteroid monotherapy.

Many doctors today prescribe oral glucocorticosteroids. While positive results can be achieved only in 15-20% of patients. Persons under 50 years of age, mainly women, respond better to such therapy if they have elevated lymphocyte counts in the lavage from the bronchi and alveoli, and also diagnosed with frosted glass changes.

Recommendations for ELISA treatment:

• Prescribing Prednisolone or another steroid drug in the same dose:
• 0.5 mg / kg body weight, once a day for 28 days.
• 0.25 mg / kg body weight, once a day for 8 weeks. (The dosage is reduced by 0.125 mg / kg per day or 0.25 mg / kg every other day.)
• Supplementing therapy with Azathioprine. The maximum daily dose is 150 mg per day. Calculate it at 2-3 mg / kg of body weight.
• Alternatively, Prednisolone therapy can be supplemented with Cyclophosphamide. Prescribed to patients at 2 mg / kg body weight. The daily dose should not exceed 150 mg. The starting dose is 25-50 mg per day. It is gradually increased by 25 mg every 1 or 2 weeks. The increase continues until the daily dose reaches the maximum.

Treatment should continue for at least six months. To assess its effectiveness, attention is paid to the symptoms of the disease, to the results of X-ray and other techniques. During treatment, you need to monitor the patient's well-being, since such therapy is associated with a high risk of complications.

Cyclophosphamide is an alkylating cytostatic that reduces the activity of the immune system by decreasing the level of leukocytes in the body. The drop in the number of lymphocytes is especially noticeable.

Azathioprine is its purine counterpart. It blocks the production of DNA, causes lymphopenia, helps to reduce T and B lymphocytes, and resists the production of antibodies and natural killer cells. Azathioprine, unlike Cyclophosphamide, does not reduce immunity so much, but helps to stop inflammation. This is possible by suppressing the production of prostaglandins, and the drug also prevents the penetration of neutrophils into the area of inflammation.

There are also specialists who oppose the use of cytostatics in the treatment of ELISA. They justify this by the fact that the likelihood of developing complications with such therapy is extremely high. This is especially true when using Cyclophosphamide. The most common side effect is pancytopenia. If platelets fall below 100,000 / ml, or the level of lymphocytes falls below 3,000 / ml, then the dosage of drugs is reduced.

In addition to leukopenia, treatment with Cyclophosphamide is associated with the development of side effects such as:

• Bladder cancer.
• Hemorrhagic cystitis.
• Stomatitis.
• Stool disorder.
• High susceptibility of the body to infectious diseases.

Azathioprine, in turn, can cause disorders in the functioning of the digestive system, and it is also a gonadal and teratotoxic drug.

If the patient was nevertheless prescribed cytostatics, then every week he will have to donate blood for a general analysis (within the first 30 days from the start of treatment). Then blood is donated 1-2 times every 14-28 days. If therapy is carried out using Cyclophosphamide, then every week the patient must bring urine for analysis. It is important to assess her condition and monitor the appearance of blood in the urine. It can be difficult to implement such control in home treatment, therefore, such a therapy regimen is not always used.

As an alternative for the treatment of ELISA, antifibrotic drugs are used, namely: Colchicine, Interferons, Pirfenidone, D-penicillamine.

D-penicillamine is the first anti-fibrotic drug to be used to treat ELISA. It prevents collagen crosslinks from forming, so fibrin cannot form. This tool shows the maximum efficiency in the treatment of fibrosing alveolitis, which develop against the background of systemic pathologies of the connective tissue. In modern practice, this remedy is not often used, since it can cause a number of side effects, for example, nephrotic syndrome. If therapy is indicated to the patient, then he is prescribed 0.3 g per day for 3-5 months, and then 0.15 g per day for 1-1.5 years.

Scientists hope that the use of interferons will help to cope with idiopathic fibrosing alveolitis. They prevent the proliferation of fibroblasts and matrix protein into lung tissue cells.

The third promising drug for the treatment of ELISA is Pirfenidone. It blocks the mitogenic effects of cytokines and reduces the production of extracellular matrix.

Another ELISA treatment option is based on the use of antioxidants, since a violation of the ratio in the "oxidants-antioxidants" system leads to damage and inflammation of the lung tissue. Patients are prescribed acetylcysteine at 1.8 g / knock for 3 months, as well as vitamin E at 0.2-0.6 g per day.

A radical way to treat pathology is lung transplantation. The survival rate of patients within 3 years after surgery is 60%. However, many patients with ELISA are in old age, so they cannot tolerate such an intervention.

Treatment of complications

If a patient develops a respiratory infection, then he is prescribed antibiotics and antimycotics. Doctors insist that such patients be vaccinated against influenza and pneumococcal infection. Therapy of pulmonary hypertension and decompensated chronic pulmonary heart disease is carried out according to the appropriate protocols.

If the patient manifests hypoxemia, then oxygen therapy is indicated. This makes it possible to reduce shortness of breath and increase the patient's exercise tolerance.

Forecast

The prognosis in patients with idiopathic fibrosing alveolitis is poor. The average life expectancy of such patients does not exceed 2.9 years.

The prognosis is somewhat better in sick women, in young patients, but only on condition that the disease lasts no more than a year. It also improves the prognosis of a positive response of the body to treatment with glucocorticosteroids.

Most often, patients die from respiratory and pulmonary heart failure. These complications develop due to the progression of ELISA. Also, death can happen due to lung cancer.

Author of the article: Alekseeva Maria Yurievna | Therapist

Education: From 2010 to 2016 Practitioner of the therapeutic hospital of the central medical-sanitary unit No. 21, city of elektrostal. Since 2016 she has been working in the diagnostic center No. 3.