home Folk remedies Treatment of idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis: modern view on pathogenesis and the role of biomarkers Idiopathic pulmonary fibrosis ICD

Treatment of idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis: modern view on pathogenesis and the role of biomarkers Idiopathic pulmonary fibrosis ICD

Idiopathic pulmonary fibrosis (IPF) is one of the most common diseases from the IIP group. The picture of IPF was described by Scadding in 1960, and he was the first to coin the term “fibrosing alveolitis.” It is possible that the earliest description of IPF was by Rindfleisch, who in 1897 described “cystic cirrhosis of the lungs,” a lung disease characterized by thickening and shrinking of the lung parenchyma and the formation of a “honeycomb lung.”

The ATS/ERS International Conciliation Document (2000) proposes the following IPF definition: IPF is a specific form of chronic interstitial fibrosing pneumonia limited to the lungs and associated with the histological appearance of usual interstitial pneumonia on surgical (thoracoscopic or open) lung biopsy.

In our country, synonyms for IPF are “idiopathic fibrosing alveolitis” (IFA) and “cryptogenic fibrosing alveolitis”, which has become more widespread in the UK. The concepts “idiopathic” and “cryptogenic”, despite a slight semantic difference, are currently considered synonyms, denoting the hidden, unclear nature of the disease.

ELISA (synonyms: Hamman-Rich disease or syndrome, Skedding syndrome, diffuse progressive interstitial fibrosis of the lungs, fibrous dysplasia of the lungs, etc.) is a unique pathological process characterized by progressive damage to the interstitial tissue of the lungs, inflammation and fibrosis of the pulmonary interstitium and air spaces, disorganization of the structural and functional units of the parenchyma, which leads to the development of restrictive changes in the lungs and impaired gas exchange.

Etiology unknown. Possible etiological factors include smoking and certain types of silicate dust. The viral nature of the disease and genetic predisposition are discussed.

Pathogenesis remains unclear. The main pathogenetic mechanism that determines the clinical picture is the development of the alveolar-capillary block. The degree of decrease in the diffusion capacity of the lungs and, accordingly, the severity of arterial hypoxemia, respiratory failure and their clinical manifestations largely depend on the degree of its severity.

The decrease in the diffusion capacity of the alveolar-capillary membrane is associated primarily with fibrosis of the interalveolar septa and the loss of respiratory functions by the alveolar epithelium due to its metaplasia into cubic. However, the resistance of the alveolar-capillary membrane to gas exchange is only half of the total diffusion resistance. The decrease in the diffusion capacity of the lungs largely depends on the degree of perfusion impairment, which is caused by a decrease in the contact surface of the alveolar air with the blood of the alveolar capillaries and a reduction in contact time. The listed mechanisms, as well as reflex constriction of pulmonary vessels due to endocapillary hypoxia, contribute to an increase in pressure in the pulmonary artery (Euler-Lillestrand reflex) and the development of cor pulmonale. The share of venoarterial shunt is relatively small - about 6%.

It is assumed that in the interstitial tissue of the lungs, collagen breakdown is reduced and its synthesis by fibroblasts and alveolar macrophages is increased. An increase in collagen synthesis is facilitated by an increase in the number of individual subpopulations of lymphocytes that react to lung tissue collagen as a foreign protein and produce lymphokines that stimulate collagen formation. It is also important to reduce the production of “inhibitory factor” by lymphocytes, which inhibits collagen synthesis under normal conditions. Many authors classify Hamman-Rich syndrome as an autoimmune disease in which the functional activity of T-suppressors is inhibited, which leads to overproduction of various classes of immunoglobulins by B-lymphocytes. Antigen-antibody complexes (AIC) formed in the blood are deposited in the walls of the small vessels of the lungs. The main reason for the long-term persistence of CEC is a defect in the functional activity of the Fc fragments of IgG. Under the influence of the CEC, lysosomal fragments of alveolar macrophages and neutrophils, damage to the lung tissue occurs, compaction, thickening of the interalveolar septa, obliteration of the alveoli and capillaries by fibrous tissue.

Currently, the most attractive hypothesis is that IPF is an “epithelial-fibroblastic” disease. According to this model, the complex interaction between epithelial cell injury and mesenchyamal cells leads to dysregulation of repair mechanisms with excess production of profibrotic cytokines, extracellular matrix, and impaired angiogenesis.

Pathological anatomy. Histological changes in lung tissue vary, which depends not only on the characteristics of the process itself in a particular patient, but also on the phase (stage) of the disease.

There are 5 degrees of pathomorphological changes in the lung tissue in patients with IPF:

I degree: swelling of the interalveolar septa, cellular infiltration, capillary tortuosity.

II degree: exudation of serous-fibrous fluid (rich in protein and stained with eosin) and cellular exudation into the alveoli, which leads to obliteration of the alveolar space (intra-alveolar fibrosis). Another way of organizing alveolar exudate is its resorption into the interalveolar septa with compaction and fibrosis of the latter. Both of these options can coexist.

III degree: involvement of bronchioles in the process with the formation of small cysts and destruction of the structure of the alveoli.

IV degree: the normal structure of the lung tissue is completely disrupted, the cystic cavities gradually increase.

V degree: the formation of the so-called “cellular (or cellular) lung.” Cysts reach 1 cm in diameter.

Clinical symptoms: ELISA is most common in the age range from 40 to 49 years. Male to female ratio 2:1

There are no pathognomonic signs of the disease characteristic only of ELISA. The onset may be imperceptible or is associated by patients with an acute respiratory infection, influenza, and is manifested by the occurrence of shortness of breath during moderate physical exertion. Steadily progressive shortness of breath- one of the most characteristic and permanent signs of ELISA. Sometimes, as the first sign of the disease, patients note a cough (dry or with scanty mucous sputum), which is then accompanied by progressive shortness of breath. As the disease progresses, the cough may intensify and be accompanied by neurological chest pain. A typical complaint is the inability to take a deep breath.

In some patients, the first manifestation of the disease may be an increase in body temperature to 38-39°C, only then shortness of breath and cough occur. About 5% of patients note periodic hemoptysis.

One of the signs of the disease, indicating (along with others) the progression of the pathological process in the lungs, is weight loss.

Arthralgia (including morning joint stiffness), muscle pain, intermittent increases in body temperature to subfebrile or febrile levels, and Raynaud's syndrome are observed in half of patients with IFA. Such a high incidence of joint damage is an additional argument for the participation of autoimmune disorders in the pathogenesis of this pathology. All patients experience weakness and fatigue.

When examining the patient, attention is drawn to cyanosis of varying degrees of severity (from acrocyanosis to diffuse). The degree of its severity depends on the severity of the disease. In the early stages of the chronic course of the disease, cyanosis may appear only during physical activity, but as the disease progresses, it intensifies. In acute forms of the disease, cyanosis is one of the early signs.

Patients notice changes in the nail phalanges associated with chronic hypoxia (symptom of “drumsticks” and “watch glasses”). The rate of formation of these symptoms depends on the activity, duration of the pathological process and the severity of respiratory failure.

When percussing the lungs over the affected area, a dullness of the percussion tone is noted (usually in the lower parts of the lungs).

During auscultation, crepitus is heard during inspiration (usually at the height of inspiration). This sound phenomenon is called “cellophane crackling” in the literature. Often this is a bilateral crepitus, best heard along the posterior and middle axillary lines, as well as between the shoulder blades. Crepitation is not always a constant symptom of ELISA. In the acute form of the disease, crepitus can be heard even with a normal x-ray picture, while at the same time it may not be present in a chronic course and changes in the x-ray; it may disappear with adequate therapy.

A characteristic auscultatory sign of IFA is weakened vesicular breathing (shortened inhalation and exhalation phases). Hard breathing and dry wheezing may occur when endobronchitis is associated. In the presence of pulmonary hypertension, an accentuation of tone II over the pulmonary artery is observed.

As the disease progresses, signs of respiratory failure and cor pulmonale appear: diffuse gray-ash cyanosis, accent II tone over the pulmonary artery, tachycardia, gallop rhythm, swelling of the jugular veins, peripheral edema (all signs of circulatory failure of the right ventricular type appear). A decrease in body weight of patients up to the development of cachexia is a characteristic sign of the terminal stage of IPF.

In which, due to fibrous changes (scars) and compaction of the lung tissue, the normal functioning of the lungs is disrupted. As the disease progresses, the lung tissue becomes increasingly scarred, which leads to a decrease in the amount of oxygen entering the blood.

The five-year survival rate of patients with IPF does not exceed 30%, and only the recent advent of antifibrotic therapy has made it possible to slow down the progression of the disease and prolong the lives of patients. Unfortunately, such therapy is not available to every Russian patient: this is due to the low level of awareness about the disease - often not only patients, but also medical specialists do not know about it. Currently, only a few hundred cases of the disease have been officially registered in Russia, but according to experts, there are more than 10 thousand such patients in the country.

Difficulties in diagnosing IPF are due to the fact that the symptoms of the disease also occur in other diseases - patients are misdiagnosed and prescribed therapy that does not alleviate their condition. About 60% of patients with IPF do not receive treatment on time.

“Diagnosis of IPF is objectively difficult,” says Alexander Averyanov, director of the Federal State Budgetary Institution Research Institute of Pulmonology of the Federal Medical and Biological Agency of Russia, Doctor of Medical Sciences, Professor. – On the one hand, its symptoms: dry cough, shortness of breath during exercise and lung sounds on auscultation, reminiscent of the crunching of cellophane, are characteristic of many other respiratory and cardiovascular diseases. However, due to the rarity and little-studied nature of the disease, most therapists and even pulmonologists do not have sufficient experience in diagnosing and treating this disease. As a result, in more than 50% of cases, patients with idiopathic pulmonary fibrosis are initially given a completely different diagnosis: COPD, heart failure - and are prescribed therapy that does not and cannot help, and in some cases even harms. From the moment you consult a doctor until the correct diagnosis is made, on average, more than a year passes, and during this time the disease progresses, fibrotic processes in the lungs increase, making breathing more and more difficult, leading to disability and early death.”

In some cases, a correct diagnosis cannot be made throughout the patient's life, leading to the disease being considered a rarer disease than it actually is. As a result, the funding available for the treatment of patients with IPF is insufficient to provide effective therapy for all patients. Traditional regimens using glucocorticosteroids and cytostatics do not give the expected results, and innovative drugs that can actually prolong life are not paid for by the state.

To raise awareness about idiopathic pulmonary fibrosis and provide care to patients, International IPF Week is being held from September 16 to 23 around the world, including Russia. Representatives of the medical community and patient organizations are interested in ensuring that as many people as possible know about the symptoms of the disease, its dangers and possible treatment. Timely administration of therapy soon after diagnosis will help prevent rapid progression of the disease and prolong the period of active life.

Men suffer from idiopathic pulmonary fibrosis much more often than women, and the mortality rate from this disease exceeds the mortality rate from many types of cancer. Men over 60 years of age, smokers (as well as those who have quit), if shortness of breath and cough occur, should contact a specialized pulmonology center to undergo an examination to rule out IPF.