Bronchiolitis obliterans is a diffuse lesion of bronchioles, leading to partial or complete obliteration of their lumen and the development of respiratory failure. Disease is manifested by weakness, fever, dry obsessive cough and increasing shortness of breath, distant wheezing, in the late period – cyanosis and “puffing” breathing. Diagnostics includes X-ray and CT of the chest organs, functional tests, histological analysis of lung tissue. Corticosteroids, mucolytics, diuretics, antioxidants, antibiotics and antiviral drugs are used in the treatment of BO.
ICD 10
J21 Acute bronchiolitis
Meaning
Bronchiolitis obliterans is an obstructive disease of the “small respiratory tract”, occurring with the defeat of terminal bronchioles – branching bronchi with a diameter of less than 3 mm, devoid of cartilaginous plates and glands. Granulation growths developing in the distal airways, alveolar passages and alveoli lead to the progression of respiratory failure, early disability and mortality. Pathology in pulmonology is quite rare: its prevalence in the pediatric population, according to various sources, varies from 0.2 to 4%. The large spread of statistical data is explained by the similarity of bronchiolitis obliterans with other respiratory diseases (bronchial asthma, bronchiectasis), as well as diagnostic difficulties.
Classification
In accordance with the clinical classification, which is based on the etiological factor, disease is divided into post-infectious, post-transplant, post-inhalation, drug-induced, idiopathic. Depending on the pathohistological changes, bronchiolitis can take an acute (exudative) or chronic (productive-sclerotic) course.
Among chronic form, proliferative (with the formation of luminal exudate, bronchiolar and alveolar Masson bodies) and constrictive (with subepithelial growth of fibrous tissue, lumen stenosis and rigidity of the bronchiole wall) are distinguished. Proliferative forms of the disease are represented by bronchiolitis obliterans with organizing pneumonia and cryptogenic organizing pneumonia; constrictive – respiratory bronchiolitis, diffuse panbronchiolitis, follicular bronchiolitis.
With bronchiolitis obliterans, inflammatory lesion of the small respiratory tract with the development of exudation, granulomatous reaction and fibrosis leads to irreversible changes in the walls of the bronchioles: concentric narrowing and obliteration of the lumen, most pronounced in the terminal areas. Disease is characterized by the presence of bronchiolar (peribronchiolar) inflammatory infiltrate from lymphocytes, macrophages and plasma cells, the development of cylindrical bronchiectasis with stagnation of secretions and the formation of mucous plugs.
With bronchiolitis, there is a decrease in pulmonary capillary blood flow (by 25-75%), which causes hypertension in the small circle of blood circulation, an increase in the load on the right half of the heart and hypertrophy of the right ventricle (“pulmonary heart“). The outcome of bronchiolitis obliterans is limited pneumosclerosis or dystrophy of lung tissue without pronounced sclerosis with a significant violation of functional pulmonary blood flow.
Causes of bronchiolitis obliterans
The polyetiological nature of the disease allows us to consider it as a manifestation of nonspecific tissue reactions of the small respiratory tract to the action of various damaging factors.
Post-infectious bronchiolitis develops more often in children and is associated with infections caused by adenovirus, respiratory syncytial virus, cytomegalovirus, parainfluenza virus, herpes. The development of acute form can also be caused by other pathogens: mycoplasma, klebsiella, legionella, fungi of the genus aspergillus, HIV.
Inhalation bronchiolitis obliterans can be caused by inhalation of toxic gases (sulfur dioxide, nitrogen dioxide, chlorine, ammonia), acid vapors, organic and inorganic dust, nicotine, cocaine. Medicinal bronchiolitis obliterans is provoked by taking certain medications (cephalosporins, penicillins, sulfonamides, amiodarone, gold preparations, cytostatics).
Idiopathic forms include cases of diseases that occur against the background of diffuse connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus), Stevens-Johnson syndrome, exogenous allergic alveolitis, aspiration pneumonia, inflammatory processes of the gastrointestinal tract (ulcerative colitis, Crohn’s disease), malignant histiocytosis, lymphoma, etc.
Posttransplantation form develops in 20-50% of patients who have undergone organ and tissue transplantation (heart-lung complex, both or one lung, bone marrow).
Bronchiolitis obliterans symptoms
The onset of bronchiolitis obliterans is acute or subacute with the development of symptoms of intoxication – weakness, malaise, high fever or subfebrile temperature. It is characterized by the presence of a dry obsessive cough, increasing expiratory dyspnea, first with physical exertion, and then with the slightest tension.
In the early stages, dry whistling, and then small bubbly wheezes are detected, often audible at a distance (remote). Later, there is a weakening of breathing, chest swelling. Hemoptysis with bronchiolitis obliterans is rarely observed. Signs of respiratory failure and pulmonary hypertension may further progress with the formation of a chronic “pulmonary heart”.
The course of pathology can be abrupt with alternating periods of deterioration and relative stabilization of the condition, but there is no improvement or resolution of the disease. In the late stages of bronchiolitis obliterans, cyanosis is noted; significant tension of the auxiliary respiratory muscles of the neck when breathing (the so-called “puffing” breathing).
Diagnostics
The diagnosis of bronchiolitis obliterans is difficult and is based on anamnesis, clinical manifestations, physical examination data, high-resolution chest X-ray and CT, functional tests (studies of blood gas composition, respiratory function, determination of nitric oxide in exhaled air), ECG and EchoCG results, cytograms of bronchoalveolar flushing, as well as histological tissue analysis easy.
A standard X-ray examination of the chest with bronchiolitis obliterans reveals hyperventilation of the lungs, weakly expressed dissemination of the focal-mesh type, a decrease in lung volume. CT of the lungs, being a more sensitive diagnostic method, allows you to detect the characteristic signs of bronchiolitis obliterans in vivo: direct (narrowing of the bronchial lumen, reniform growths, peribronchial thickening and bronchiolectasis) and indirect (mosaic decrease in transparency, over-transparency of the affected areas of the bronchioles, signs of “pseudomatous glass”, changes in lung tissue distal to the site of obliteration).
ECG and EchoCG data indicate the presence of symptoms of pulmonary hypertension, the formation of a chronic “pulmonary heart”. Obstructive respiratory dysfunction and signs of hyper–airiness of the lungs are noted with constrictive bronchiolitis obliterans; restrictive type of violation of the FER and a decrease in the diffusion capacity of the lungs – with proliferative bronchiolitis obliterans. A decrease in gas exchange is expressed in a reduced content of oxygen and carbon dioxide in arterial blood (hypoxemia and hypocapnia).
The most informative method of diagnosing bronchiolitis obliterans remains a transbronchial and thoracoscopic biopsy with histological examination of a lung biopsy, which allows to identify the existing proliferative-sclerotic changes. Differential diagnosis of bronchiolitis obliterans with chronic bronchitis, fibrosing alveolitis, obstructive pulmonary emphysema, bronchial asthma should be carried out.
Bronchiolitis obliterans treatment
The difficulties of early diagnosis, rapid progression and irreversibility of changes in the bronchial wall severely limit the possibilities of treatment, which is reduced to preventing further development of the inflammatory process and fibrous proliferation in the small airways and stabilizing the patient’s condition.
The main medications for bronchiolitis obliterans are corticosteroids – most often prednisone (dexamethasone), sometimes in combination with immunosuppressants (cyclophosphane). Inhalation therapy with budesonide, fluticasone, beclomethasone reduces the need for systemic glucocorticoids by achieving higher concentrations of the drug in tissues. With the infectious genesis of bronchiolitis obliterans, antiviral and antibacterial agents are used in the acute phase of the disease.
With increased bronchial obstruction, mucolytic drugs are prescribed (ambroxol by inhalation or enterally), beta2-adrenomimetics (salbutamol); with pulmonary hypertension – diuretics (furosemide, spironolactone), methylxanthines (eufillin), sildenafil, prostacycline analogues (iloprost), ACE inhibitors (captopril); with the development of hypoxemia – oxygen therapy. In the treatment of bronchiolitis obliterans, antioxidants (coenzyme Q10, maldonium) are used in combination with vitamins, physiotherapy, chest massage, bronchoalveolar lavage.
Forecast
Bronchiolitis obliterans is a rapidly progressive disease, usually with an unfavorable prognosis. It is complicated by the development of emphysema of the lungs, hypertension of the small circulatory circle, increasing pulmonary and heart failure. Even adequate pharmacotherapy of obliterating bronchiolitis does not allow restoring the normal morphofunctional state of the respiratory tract and lung tissue. it is manifested by weakness, fever, dry obsessive cough and increasing shortness of breath, distant wheezing, in the late period – cyanosis and “puffing” breathing. Diagnostics includes X-ray and CT of the chest organs, functional tests, histological analysis of lung tissue. Corticosteroids, mucolytics, diuretics, antioxidants, antibiotics and antiviral drugs are used in the treatment of bronchiolitis obliterans.
Literature
- Bronchiolitis obliterans: an update. Chan A, Allen R. Curr Opin Pulm Med. 2004 Mar;10(2):133-41. link
- [Anatomoclinical diversity of bronchiolitis obliterans after lung transplantation. Anatomical study of 16 cases among 64 transplantations]. Loire R, Brune J, Cordier JF, Mornex JF, Philit F, Roux N, Tabib A. Arch Anat Cytol Pathol. link
- Bronchiolitis obliterans and airways obstruction associated with graft-versus-host disease. Epler GR. Clin Chest Med. 1988 Dec;9(4):551-6. link
- Diagnosing and managing bronchiolitis obliterans in children. Kavaliunaite E, Aurora P. Expert Rev Respir Med. 2019 May;13(5):481-488. link
- Bronchiolitis obliterans syndrome is not specific for bronchiolitis obliterans in pediatric lung transplant. Towe C, Chester Ogborn A, Ferkol T, Sweet S, Huddleston C, White F, Faro A. J Heart Lung Transplant. 2015 Apr;34(4):516-21. link
