Pneumonitis in adults and children

Pulmonologists attribute pneumonitis to interstitial lung diseases, a distinctive feature of which is damage to the tissues that support the intralobular air exchange part of the lungs and form its most important structures - the alveoli.

Epidemiology

The real statistics of pneumonitis are unknown. According to some reports, the prevalence of idiopathic interstitial pneumonia (which is defined by many as idiopathic pneumonitis) per 100 thousand of the population of the European continent and North America is estimated at 7-50 cases with a tendency to constantly increase. [1]

The chronic form of pneumonitis is observed in almost 5% of patients with this disease.

Up to 10% of SLE patients suffer from acute lupus pneumonitis. And radiation or radiation pneumonitis after radiation therapy for advanced lung cancer occurs in three out of ten patients. [2]

According to WHO, pneumonitis is one of the three leading causes of death in the elderly from respiratory failure. [3]

Causes pneumonitis

Due to the lack of terminological unambiguity, some doctors continue to interpret the name "pneumonitis" as a general designation of inflammatory processes in the lungs, but one should immediately clarify what is the difference between pneumonitis and pneumonia. First of all, these are etiological differences: if inflammation in pneumonia is caused by an infection - bacterial, viral or fungal, then in pneumonitis the causes are not associated with these infections, and the inflammation is immunologically mediated. Thus, viral pneumonitis as a diagnosis contradicts the pathogenetic essence of the disease identified by researchers, and publications on pneumonitis arising from infection by viruses (RSV, Varicella Zoster, HSV or Cytomegalovirus) refer to the 70-90s of the last century.

It is also necessary to take into account the features of alteration of the lung tissue: inflammation in cases of pneumonia has an exudative character with infiltration of the parenchyma, and pneumonitis is characterized by fibrous changes in the tissues of the alveolar and intralobular interstitium.

Depending on the etiology, there are types or types of this pulmonary disease, including pneumonitis in children, which develop for the same reasons.

Inflammation of the interstitium caused by the immune response to long-term inhaled substances in the air (aeroallergens) is defined as hypersensitive pneumonitis or hypersensitive pneumonitis; a simpler definition is allergic pneumonitis, which is often called  exogenous allergic alveolitis . Dust containing animal or plant proteins (inhaled during agricultural and other work) can be triggers of the immune response leading to damage to the pulmonary interstitium. This type includes the so-called "bird lover's lung" - the result of an immune response to the proteins of bird feathers and their dry droppings. [4]

If serologic testing of peripheral blood reveals an increased level of eosinophils involved in the hypersensitivity reaction  , specialists may determine eosinophilic pneumonitis (also called Loeffler's syndrome or  acute eosinophilic pneumonia ) or hypersensitivity reactive pneumonitis. When low molecular weight chemicals present in the air - gaseous or in the form of aqueous dispersions - are inhaled, chemical pneumonitis is diagnosed. And with  lesions of the lungs caused by inhalation of toxic substances , toxic pneumonitis can develop. [5]

What is drug pneumonitis, in more detail in the publication -  Drug lesions of the lungs . For example, pneumonitis is one of the side effects of anticancer drugs such as Azathioprine, Nivolumab, Cyclophosphamide, Tocilizumab, Procarbazine, etc. In addition, foreign experts isolate immune pneumonitis, a side effect of cancer immunotherapy using the so-called immune checkpoint inhibitors: drugs Ipilimumab and Tremelimumab.

Separately, aspiration pneumonitis is isolated, provoked by the ingress of stomach contents into the lower respiratory tract (Mendelssohn's syndrome or acid-aspiration pneumonitis caused by food, which often accompanies myasthenia gravis of the pharynx), as well as arising after nasogastric intubation or during general anesthesia that causes vomiting. [6]

Obstructive pneumonitis is most commonly associated with obstruction of the airways by a tumor, for example, in patients with squamous cell lung cancer.

Due to the effect of ionizing radiation on the lungs - with radiation therapy of malignant neoplasms in the mediastinal region - there is radiation pneumonitis; other definitions are post-radiation or radiation pneumonitis.

Desquamative or destructive pneumonitis - with a violation of the structure of the interstitium - can have any etiology, including long-term smoking. [7]

Patients with autoimmune diseases have nonspecific pneumonitis. So, with a diffuse autoimmune disease of connective tissue - systemic lupus erythematosus - in almost half of the cases, acute or chronic lupus pneumonitis or lupus pneumonitis is observed. [8]

Such a complication of the terminal stage of progressive kidney failure, such as uremic pneumonitis, is associated with diffuse violations of the permeability of alveolocapillary membranes, as well as interstitial and intraalveolar edema against the background of a decrease in blood coagulation factors due to the high content of metabolic products of amino acids and proteins - urea nitrogen.

Quite often, the causes of pneumonitis cannot be clarified, and then idiopathic pneumonitis is diagnosed, which can be called  idiopathic fibrosing alveolitis .

Risk factors

The main risk factors for developing pneumonitis include:

• smoking;
• agriculture-related professions (grain harvesting, hay making, poultry farming);
• tendency to allergic reactions;
• exposure to various substances in the air (in the workplace or in the environment);
• long-term use of certain drugs;
• chemotherapy, immunotherapy, and radiation therapy for cancer;
• the presence of systemic autoimmune diseases.

The risk of aspiration from the stomach into the lungs and the development of aspiration pneumonitis is increased with trauma, epileptic seizures, esophageal motility disorders, and severe gastroesophageal reflux. [9]

Pathogenesis

In pneumonitis, the pathogenesis of lesions of the connective tissue interstitium, elastic walls of the alveoli and interalveolar septa is caused by a violation of their structure at the cellular level and progressive fibrosis.

The interstitium consists of fibers (elastic and collagen), fibroblasts, connective tissue macrophages (histiocytes), neutrophils, and some other cellular components.

The reaction of autoimmune antibodies to the antigen leads to an increased division of effector T cells - T-helper lymphoid cells of the second type (Th2), which stimulate the cellular immune response to non-microbial foreign substances that are allergens.

The answer lies in the stimulation of pro-inflammatory cytokines, chemokines, NK and B-lymphocytes of the tissues of the alveolar interstitium and an increase in the activity of transforming growth factor (TGF-β) and fibroblast growth (FGFR1-3). This causes an intensive proliferation of common fibroblasts, as well as a multiple increase in the number of myofibroblasts (smooth muscle fibroblasts) present in the lung tissues, which produce proteins and proteases of the extracellular matrix. [10]

Symptoms pneumonitis

On the basis of symptoms and data of instrumental diagnostics, acute, subacute and chronic pneumonitis is classified.

As a rule, the first signs of pneumonitis are dyspnea (shortness of breath) and a dry, hacking cough.

Pneumonitis can develop differently in different patients, but the most common symptoms are:

• difficulty breathing;
• discomfort in the mediastinal area;
• general weakness and increased fatigue;
• loss of appetite and unexplained weight loss;
• pulmonary bleeding.

In acute interstitial pneumonitis, the cough may be with discharge of thick mucous phlegm, and breathing difficulties in many cases progress rapidly, leading to severe respiratory failure at a later stage.

Bilateral or bilateral pneumonitis develops when the alveolar interstitium of both lungs is damaged.

In addition to shortness of breath and cough, symptoms of radiation pneumonitis are fever, heaviness in chest pain.

In lupus pneumonitis, there is a nonproductive cough with bleeding.

Pneumonitis in lung cancer is manifested by a prolonged cough with shortness of breath and hoarseness of the voice, as well as chest pain (especially severe with a deep breath). And with a certain localization of the primary tumor or its growth, obstructive pneumonitis may develop in lung cancer with a decrease in its volume -  lung atelectasis , which leads to the development of respiratory distress syndrome. [11]

Complications and consequences

Why is pneumonitis dangerous? In the absence of treatment or its late onset, pneumonitis can give such complications and consequences as:

• irreversible damage to the pulmonary alveoli in the form of pulmonary fibrosis, as well as  pneumosclerosis ;
• pulmonary hypertension;
• right ventricular heart failure (cor pulmonale);
• respiratory failure, lung failure and death.

Diagnostics pneumonitis

Clinical diagnosis of pneumonitis involves a complete history and extensive  examination of the respiratory system .

Necessary tests include a general and biochemical blood test; immunological blood test - for antigen-specific IgG antibodies and other  circulating immune complexes in the blood .

Held  diagnostic bronchoalveolar lavage  (rinsing) and laboratory investigation of the recovered liquid.

Instrumental diagnostics uses functional pulmonary tests (spirometry and oximetry), x-rays and  computed tomography of the chest  (CT). In doubtful cases, endoscopic bronchoscopy with pulmonary biopsy is needed. [12]

Computed tomography gives much more detailed information about changes in the lungs than conventional radiography, and pneumonitis on CT of the lungs is visualized in the form of varying degrees of increase in the thickness of the walls of the alveoli and the septa between them. At the same time, the opacity and compaction of the interstitium resembles frosted glass, and the pattern of the lungs resembles honeycomb cells (due to small foci of fibrosis).

Differential diagnosis

Hypersensitivity pneumonitis can be similar to some infectious and fibrotic lung diseases. Therefore, the differential diagnosis of pneumonitis is carried out with obliterating bronchiolitis, bronchial asthma and  bronchiectasis ; infectious interstitial pneumonia and  pneumoconiosis ; idiopathic fibrosis, hemosiderosis and alveolar proteinosis of the lungs; granulomatous lung diseases (sarcoidosis, beryllium disease, mycobacterial infections), Churge-Strauss syndrome; carcinomatous lymphangitis and sarcoidosis. [13], [14]

In many cases, pneumonitis and alveolitis are considered synonymous, for example, allergic alveolitis and hypersensitivity (allergic) pneumonitis in all respects are one and the same disease. [15]

Pneumonia or pneumonitis with covid coronavirus?

The cause of COVID-19 is infectious caused by the SARS-CoV-2 virus. The most common complication is viral interstitial pneumonia, with a high likelihood of acute respiratory distress syndrome and subsequent respiratory failure.

At the same time, pneumonia in covid coronavirus has similar symptoms and results of CT scan of the lungs with acute hypersensitive pneumonitis and immune pneumonitis (associated with the treatment of cancer with immune checkpoint inhibitors), which, without thorough testing for the CoV-2 virus, complicates the diagnosis.

Pneumonia in  COVID-19  is manifested by fever and coughing, and respiratory distress syndrome develops later. With pneumonitis, shortness of breath and cough immediately appear, but fever is extremely rare.

More information in the material -  Coronavirus infection (atypical pneumonia): causes, symptoms, diagnosis, treatment

Treatment pneumonitis

The most common treatment for pneumonitis is the use of systemic corticosteroids that promote immunosuppression. Oral corticosteroids are prescribed Prednisolone or Methylprednisolone (standard dosage - 0.5 mg / kg body weight for two to four weeks. Long-term use of corticosteroids increases the risk of infections and can lead to osteoporosis.

Reduce the formation of antibodies immunosuppressants Mycophenolate mofetil (Supresta, MMF-500), Anakinra (Kinneret), Pirfenidon (Esbriet). Side effects of Anakinra are manifested by headache, leukopenia and thrombocytopenia. The immunity-lowering agent Pirfenidone is contraindicated in liver and kidney failure. And among its side effects, the instructions indicate headache and dizziness; nausea, vomiting, and diarrhea / constipation; decreased appetite and body weight; pain in the hypochondrium, joints and muscles; hyperemia of the skin with rashes and itching. [16]

Other drugs are also used, in particular, an inhibitor of fibroblast growth factor receptors and transforming growth factor Nintedanib (Vargatef, Ofev) in capsules for oral administration. This remedy can cause nausea, vomiting, diarrhea, abdominal pain, impaired appetite, increased levels of liver transaminases. 

Treatment of radiation pneumonitis is carried out by GCS, decongestants and drugs that dilate the bronchi.

Breathing problems require oxygen therapy, and in severe cases, artificial ventilation. [17]

Patients with progressive hypersensitive pneumonitis with ineffectiveness of conservative therapy and the threat of lethal respiratory failure are shown surgical treatment -  lung transplantation .

Prevention

Hypersensitivity pneumonitis can be prevented by avoiding known irritants - protecting the airway from dust while working with a respirator.

But in many cases, if the antigen is not detected, the prevention of respiratory contact is problematic.

Forecast

The stage and severity of pneumonitis determine its prognosis. In mild acute hypersensitivity pneumonitis, lung function is most often restored after treatment. And the chronic form of the disease leads to fibrosis, the terminal stage of which can end in severe respiratory failure and, as a result, death (in almost 60% of cases).