Interstitial lung processes

Interstitial lung processes (IPP, also fibrotic lung processes ) are immunopathological processes at the level of the lung interstitium, ie in the interalveolar area, in the alveoli and in the peribronchium. They prevent efficient gas exchange at the alveolar-capillary membrane and lead to respiratory insufficiency.

This is a group of diseases of various etiologies, which are characterized by varying degrees of inflammatory and / or fibrotic involvement of the lung parenchyma. Lung involvement is usually manifested by exertional dyspnea, weight loss, subfebrile illness, and more frequent respiratory infections. develops cor pulmonale with signs of right heart decompensation.

Classification

 * 1) Diffuse lung processes for known causes : exogenous allergic alveolitis (EAA), pneumoconiosis, post-radiation pneumonia, drug-induced lung damage (eg amiodarone and methotrexate);
 * 2) Idiopathic interstitial pneumonia : idiopathic pulmonary fibrosis (IPF); nonspecific interstitial pneumonitis; lymphocytic interstitial pneumonitis; desquamative interstitial pneumonitis; interstitial lung disease associated with respiratory bronchiolitis; cryptogenic organizing pneumonia; acute interstitial pneumonitis;
 * 3) Granulomatoses - sarcoidosis, pulmonary histiocytosis from Langerhans cells , granulomatosis with polyangiitis, etc. vasculitis, etc .;
 * 4) Other : eosinophilic pneumonia, lymphangioleiomyomatosis, alveolar proteinosis, etc.

Pathogenesis
deposition along the alveolar walls plays a role in the pathogenesis Fibrin → so-called hyaline membranes are formed in the alveoli. This is followed inflammatory phase infiltrated by neutrophils (later macrophages and lymphocytes), which mediate repair processes resulting in fibrosis. Another pathogenetic event is alveolar cell proliferation, organization of fibrinous exudate, collagen deposition → repair / fibrosis.

Consequences of interstitial lung diseases

 * Hypoxemia (↓ p and O 2 ) especially exertional already in the initial stages with hyperventilation with a tendency to respiratory alkalosis (↓ p and CO 2 );
 * later resting hypoxemia (↓ p and O 2 ) and hypoventilation;
 * pulmonary hypertension → cor pulmonale.

Common features
Common features include exertional and then restful shortness. ISTs are often accompanied by an irritating cough. Reticulonodulation or honeycomb lungs. in the listening finding crepitations.

Examination
In laboratory diagnostics, we choose examinations to exclude damage to other organs, basic immunological examinations, examinations of autoantibodies. In indicated cases, exclusion of glomerular involvement, calcium metabolism and serum angiotensin converting enzyme in patients with suspected sarcoidosis were indicated in the screening. It is important to examine lung functions and respiratory parameters at rest, if necessary. under load and a chest skiagram in two projections (however, a negative finding does not rule out IPP!). diagnostics computed tomography high-resolution From invasive examinations, bronchoscopy with bronchoalveolar lavage and transbronchial biopsy, event. surgical lung biopsy.

Therapy
We choose therapy according to etiology (if known). The first step is to stop exposure to harmful inhalants.

Pharmacotherapy

 * systemic corticotherapy at doses appropriate to the severity of the disability
 * indications: idiopathic nonspecific interstitial pneumonitis (NSIP), severe exogenous allergic alveolitis (EAA), drug-induced lung disease, eosinophilic pneumonia, cryptogenic organizing pneumonia (COP), sarcoidosis with lung function impairment;
 * systemic corticosteroid therapy in combination with other immunosuppressants (eg methotrexate, azathioprine, cyclophosphamide)
 * systemic connective tissue diseases, other autoimmune syndromes;
 * N-acetylcysteine ​​- idiopathic pulmonary fibrosis (IPF),
 * proton pump inhibitors - IPF,
 * inhalation bronchodilators - silicosis, coal mine pneumoconiosis,
 * inhaled corticosteroids - sarcoidosis with bronchial hyperreactivity,
 * macrolides - some forms of organizing pneumonia.

Non-pharmacological treatment

 * oxygenoterapie,
 * balneotherapy,
 * physiotherapy,
 * lung transplantation.

Prognosis
Idiopathic pulmonary fibrosis (IPF) has the most serious prognosis - lung transplantation, event. treatment with pirfenidone (immunosuppressant - suppresses fibroblast proliferation, production of proteins associated with fibrosis and cytokines and increased biosynthesis and accumulation of the extracellular matrix in response to cytokine growth factors).

Idiopathic pulmonary fibrosis (IPF)
It is a diffuse, primarily fibrotic lung process.

Pathogenesis
This is probably a uniform pathological response of lung tissue to both infectious and non-infectious agents. These cause damage to the lining of the alveoli and thus result in progressive and uncontrollable scarring. As such, the inflammatory reaction may occur only secondarily.

Epidemiology

 * Patients are most often between the ages of 40 and 70.
 * The incidence is 7.4 / 100,000 for women and 10.7 / 100,000 for men.
 * It occurs sporadically, is equally widespread in all localities, and familial cases are rare.
 * The disease is practically incurable, and even with adequate treatment, survival usually does not exceed 3-5 years.

Clinical picture

 * Beginning - prolonged unproductive cough in time with worsening exertional dyspnea, fatigue, weight loss, tachypnoea ;
 * on the bases of the lungs late inspiratory crepitus similar to velcro opening ;
 * eventually chronic hypoxia with cyanosis develops.
 * In 2/3 of patients there are club-shaped fingers with nails in the shape of a watch glass.
 * Image COPD without obstructive defect, in the later phase restrictive lung damage - reduction of FVC.
 * Despite the typically protracted gradually worsening course, some patients may experience acute exacerbations:
 * sudden clinical deterioration;
 * decreased lung function;
 * radiological image of the so-called milk glass (indicates alveolitis).

Diagnostics
Here, HRCT is crucial, and a typical clinical finding does not require a biopsy if systemic connective tissue diseases and an exogenous cause are ruled out.


 * HRCT image of the lungs: pulmonary fibrosis with an image of the honeycomb lung in the bases of the lungs and minimal districts of active changes.
 * Histology from lung biopsy.
 * In patients unable to undergo surgical biopsy, X-ray and bronchoscopy must be sufficient.
 * X-ray: increased lung pattern to reticulation - honeycomb lungs.
 * Functional examination: restrictive ventilation disorder, pulmonary compliance disorder.

Therapy
Summary video
 * Anti-inflammatory and immunosuppressive drugs are ineffective because the main pathological mechanism here is pathological fibroproduction, so they are not used in treatment today.
 * Pirfenidone - inhibits fibrosis, indicated in patients with FVC 50-80%. Dosage 3x3cps - a total of 2403 mg.
 * Nintedanib - tyrosine kinase inhibitor for VEGFR, FGFR and PDGFR
 * Early alveolar lesions: N-acetylcysteine ​​3 times 600 mg (antioxidant effect).
 * Acute exacerbations: high doses of corticoids, anticoagulant therapy and antibiotics. are given to prevent exacerbations PPIs (proton pump blockers)
 * Advanced hypoxemia: long-term home oxygen therapy and consideration of lung transplantation.
 * Corticosteroids in long-term therapy are ineffective because fibrotization is not induced by an inflammatory response.

Exogenous allergic alveolitis (EAA)
Exogenous allergic alveolitis (or also hypersensitivity pneumonitis, farmer's lung, pigeon's lung) includes a group of immunologically conditioned diseases ( type III hypersensitivity ) with granulomatous inflammation in the bronchioles + alveoli. It is an interstitial pulmonary fibrosis caused by repeated contact with a certain allergen. The most endangered group are workers in plant and animal production after repeated exposures to moldy hay, straw and grain. Exogenous allergic alveolitis also occurs when working with moldy malt, furs, moldy cheeses, feathers and bird excrement. It is rare in children, it is most often caused by inhalation of organic dust from birds (pigeons, parrots, budgies).

Diagnostics

 * History, laboratory signs of inflammation, precipitating antibodies (specific IgG ) in serum against the inducing antigen ,
 * X -ray: reticulonodular drawing with mottled volatile infiltrates,
 * BAL: usually lymphocytic alveolitis, ↓ CD4 / CD8,
 * chronic phase: X-ray + HRCT image of interstitial pulmonary fibrosis / honeycomb lung; restriction, pulmonary diffusion capacity disorder, hypoxemia; lung biopsy.

Clinical picture

 * Acute

The acute form is reversible and develops within about 6 hours after intense antigen exposure. It expires within 48 hours. is physically demonstrable crepitus above the lung bases. The following manifestations are characteristic:


 * whooping cough, fever , chills, chills, malaise, myalgia, headache.


 * Chronic

If antigen exposure persists, a chronic form of exogenous allergic alveolitis develops. Lower concentrations of the relevant antigen are also sufficient for repeated exposure. Irreversible interstitial lung fibrosis (restriction disorder) occurs. Symptoms:


 * weight loss, fatigue, cough, shortness and cyanosis, cor pulmonale , clubbed fingers , eventually respiratory failure.

Therapy

 * Elimination of antigens - necessary permanent exclusion of the worker from exposure (for occupational diseases),
 * corticoids ,
 * oxygenoterapie.

Occupational pneumoconiosis
Pneumoconiosis is a group of occupational diseases caused by long-term inhalation of air containing specific inorganic particles. The basis of lung changes is the response of immunocompetent cells to these particles, which leads to damage to the lung interstitium.

Types of diseases
Silicosis


 * Silicosis ,
 * asbestosis ,
 * pneumoconiosis ,
 * beryliosis ,
 * talkose - occurs after exposure to talc dust (during its mining and grinding), possible images of the disease:
 * nodular lesions,
 * diffuse interstitial fibrosis,
 * granulomatous reactions around foreign bodies,
 * pulmonary involvement during inhalation of hard metals - cobalt, tungsten, carbide, possible pictures of the disease:
 * chronic diffuse inertia with pulmonary fibrosis,
 * acute and subacute interstitial disability with EAA or BOOP,
 * obstructive pulmonary disease resembling occupational asthma.

Nowadays, we encounter these diseases rather rarely (the incidence decreases due to prevention in the work environment).

Types of changes
The nature of the inflammatory changes depends on the shape and size of the inhaled particles, the length and intensity of the exposure. Inorganic particles can be divided into fibrogenic (silicosis, asbestosis) and non-fibrogenic (other) in terms of shape. In general, diseases caused by fibrogenic particles are worse because they do not respond to anti-inflammatory treatment and thus tend to progress permanently and their prognosis is very poor.

Manifestations of the disease
Gradual decrease in lung function, worsening cough, dyspnoea and development of respiratory insufficiency.

Diagnostics

 * History - symptoms (cough, shortness of breath), work and social history,
 * X-ray of the lungs,
 * functional lung examination ( spirometry ),
 * BAL - if we need a certificate of inorganic particles,
 * biopsies are usually no longer performed.

Therapy

 * Disease prevention (protective equipment, work environment limits),
 * elimination of additional exposure,
 * therapy of onset infections,
 * long-term home oxygen therapy (DDOT),
 * respiratory rehabilitation,
 * lung transplantation (in indicated cases).

Pulmonary manifestations in systemic connective tissue diseases
Systemic connective tissue diseases are autoimmune diseases with multiorgan involvement due to vasculitis; frequent arthritis, muscle + skin disorders. The fibrotic alveolitis is a response to immunocomplexes deposited in pulmonary capillaries. The treatment is corticotherapy.


 * Rheumatoid arthritis




 * Interstitial disability in 1.5 to 4.5%;
 * clinically and histologically identical to KFA;
 * prognosis: unfavorable in case of pulmonary changes;
 * therapy: glucocorticoids + immunosuppressants.


 * Systemic lupus erythematosus


 * Pulmonary disability in 50 to 60%: no. pleurisy, IPP , rarely acute pneumonia;
 * ray: reticulonodular shadows with max. Lower lung field involvement;
 * therapy: corticoids + penicillamine / cyclophosphamide;
 * survival 10 to 14 years (cause of death renal failure, endarteritis or sec. pneumonia).


 * Scleroderma (progressive systemic sclerosis)


 * IPP up to 80% pac.


 * Polymyozitida, dermatomyozitida
 * Sjögrenův syndrome
 * m. Bechtěrev
 * m. Crohn

Postradiation lung fibrosis
Pulmonary fibrosis represents the final stage of post-radiation lung changes.


 * After irradiation of lung tissue with ionizing radiation at doses> 8 Gy in 30 weeks,
 * ionizing radiation caused by necrotic changes healed by a fibrotic scar ,
 * clinically: dry cough, worsening dyspnoea (restriction disorder with ↓ diffusion),
 * diff. dg .: radiation pneumonitis (exudative alveolitis from pneumocyte + endothelial damage),
 * th .: in small infiltrates without treatment, in symptomatic corticoids.

Drug pulmonary fibrosis
pulmonary fibrosis is called the development of interstitial pneumonia and fibrosis within the hypersensitivity or toxic effect of the drug (bleomycin, MTX , amiodarone , nitrofurantoin inhalation of O 2 in high concentrations):


 * hypersensitivity: ATB (penicillin, ampicillin, nitrofurantoin), some cytostatics (MTX),
 * direct toxicity: cytostatics (bleomycin, cyclophosphamide ) → cytostatic lungs.

It can appear as an acute or chronic condition.

Clinical picture

 * Shortness of breath ,
 * dry, irritating cough ,
 * X-ray: localized / diffuse interstitial involvement, late honeycomb lung.

Therapy

 * Drug omission, glucocorticoids.

Related articles

 * Idiopathic pulmonary fibrosis • Rheumatoid arthritis • Systemic lupus erythematosus • Scleroderma • Sjögren's syndrome
 * Respiratory restriction