Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) is the most common form of idiopathic interstitial pneumonia, corresponding to progressive pulmonary fibrosis and predominant in male smokers. Symptoms of idiopathic pulmonary fibrosis develop over a period of several months to several years and include shortness of breath when exercising, coughing and small bubbling rales.

The diagnosis is established when analyzing the history, physical examination, chest radiography, and pulmonary function tests and is confirmed by the results of HRCT, lung biopsy or, if necessary, both methods. No specific treatment for idiopathic pulmonary fibrosis has been shown to be effective, but glucocorticoids, cyclophosphamide, azathioprine or combinations thereof are often prescribed. In most patients, deterioration occurs even against the background of treatment; median survival - less than 3 years from the date of diagnosis.

[1], [2], [3], [4], [5], [6]

Causes of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis, defined histologically as ordinary interstitial pneumonia, is 50% of cases of idiopathic interstitial pneumonia and occurs in both men and women aged 50-60 years in a 2: 1 ratio. Continuing or previous smoking in a pronounced degree correlates with the disease. There is some genetic predisposition: a family history is weighed down in 3% of cases.

Although idiopathic pulmonary fibrosis is called pneumonia, inflammation probably plays a relatively minor role. Ecological, genetic or other unknown factors are believed to initially damage the epithelium of the alveoli, but the proliferation of specific and aberrant interstitial fibroblasts and mesenchymal cells (with collagen deposition and fibrosis) is probably the basis of the clinical development of the disease. The key histological criteria are subpleural fibrosis with foci of proliferation of fibroblasts and areas of severe fibrosis alternating with regions of normal lung tissue. The widespread interstitial inflammation is accompanied by lymphocytic, plasmacytic and histiocytic infiltration. Cystic dilatation of peripheral alveoli ("cellular lung") is found in all patients and increases as the disease progresses. A similar histological structure is infrequent in IBLARB of a known etiology; the term conventional interstitial pneumonia is used for idiopathic lesions that do not have an obvious cause.

[7], [8], [9], [10], [11]

Symptoms of idiopathic pulmonary fibrosis

Symptoms of idiopathic pulmonary fibrosis usually develop for 6 months to several years and include shortness of breath during exercise and an unproductive cough. Common symptoms (fever to subfebrile digits and myalgia) are rare. The classic sign of idiopathic pulmonary fibrosis is sonorous, dry bilateral basal inspiratory small bubbling rales (resembling sound when opening a Velcro fastener). Thickening of the terminal phalanges of the fingers is present in approximately 50% of cases. The remaining results of the examination remain normal until the development of the terminal stage of the disease, when manifestations of pulmonary hypertension and systolic dysfunction of the right ventricle may develop.

Diagnosis of idiopathic pulmonary fibrosis

The diagnosis is based on the analysis of anamnestic data, the results of radiation research methods, lung function tests and biopsy. Idiopathic pulmonary fibrosis is usually mistakenly diagnosed as other diseases having similar clinical manifestations, such as bronchitis, bronchial asthma or heart failure.

When chest radiographs are usually detected diffuse enhancement of the pulmonary pattern in the lower and peripheral zones of the lung. Small cystic enlightenments ("honeycomb lung"), dilated respiratory tract due to the development of bronchiectasis can be additional findings.

Lung function tests typically exhibit a restrictive nature of the changes. The diffusion capacity for carbon monoxide (DI_CO) is also reduced. Investigation of arterial blood gases reveals hypoxemia, which is often amplified or detected during physical exertion and low values of CO concentration in the arterial blood.

HRCT allows detecting diffuse or focal subpleural strengthening of the pulmonary pattern with asymmetrically thickened interlobular septa and intralobular thickenings; subpleural changes in the form of honeycomb and traction bronchiectasis. Changes in the type of frosted glass, which capture more than 30% of the lung, indicate an alternative diagnosis.

Laboratory studies play a minor role in diagnosis. Increased ESR, C-reactive protein concentrations and hypergammaglobulinemia are often found. Concentrations of antinuclear antibodies or rheumatoid factor are increased in 30% of patients and, depending on specific values, can exclude connective tissue diseases.

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Treatment of idiopathic pulmonary fibrosis

None of the specific treatment options demonstrated efficacy. Supportive treatment of idiopathic pulmonary fibrosis is reduced to inhalation of oxygen during hypoxemia and prescriptions of antibiotics for the development of pneumonia. The terminal stage of the disease may require individual patients to perform lung transplantation. Glucocorticoids and cytotoxic agents (cyclophosphamide, azathioprine) are traditionally prescribed to patients with idiopathic pulmonary fibrosis empirically, in an attempt to stop the progression of inflammation, but only a limited amount of evidence indicates their effectiveness. However, a common practice is to try to prescribe prednisolone (orally, at a dose of 0.5 mg / kg to 1.0 mg / kg, once a day for 3 months, then lowering the dose to 0.25 mg / kg, once per day for the next 3-6 months) in combination with cyclophosphamide or azathioprine (orally, at a dose of 1 mg / kg to 2 mg / kg, once a day and N-acetylcysteine 600 mg 3 times a day as an acti- antioxidant ). With periodicity from every 3 months to 1 time per year, a spinal, radiological and physical assessment of the condition and correction of doses of drugs are performed. Treatment of idiopathic pulmonary fibrosis ceases in the absence of an objective response.

Pyrfenidone, which is a collagen synthesis inhibitory agent, can stabilize lung function and reduce the risk of exacerbations. The effectiveness of other antifibrotic agents, in particular, inhibiting the synthesis of collagen (relaxin), growth factor (suramin) and endothelin-1 (an angiotensin receptor blocker) has been demonstrated only in vitro.

Interferon-y-lb showed good effects when administered in conjunction with prednisolone in a small study, but a large, double-blind, multinational, randomized trial did not reveal its effect on long-term disease-free survival, lung function, or quality of life.

Lung transplantation is successful in patients with terminal stage of idiopathic pulmonary fibrosis who are not suffering from concomitant pathology, at the age of 55 years or less (<40% of all patients with idiopathic pulmonary fibrosis).

Forecast

Most patients have mild and severe clinical manifestations at the time of diagnosis; often the disease idiopathic lung fibrosis progresses despite treatment. Normal values of PaO2 at the time of diagnosis and fewer fibroblastic foci detected by histological examination of biopsy material improve the prognosis of the disease. On the contrary, the prognosis is worse in the elderly and worse with a decrease in lung function at the time of diagnosis and severe dyspnoea. Median survival is less than 3 years from the date of diagnosis. An increase in the frequency of hospitalizations for sudden infections of the respiratory tract and pulmonary insufficiency indicates a rapid death in the patient, which requires planning care for him. Lung cancer is more common in patients with idiopathic pulmonary fibrosis, but the cause of death is usually respiratory failure, respiratory tract infection or heart failure with ischemia and arrhythmia.

[16], [17]