OVERVIEW
An umbrella term for a group of diffuse lung diseases that primarily involve the interstitial and alveolar spaces of the lungs, resulting in the loss of alveolar-capillary functional units, which may manifest as progressive dyspnea, restrictive ventilatory dysfunction with reduced diffusion, and hypoxemia. Most of these diseases have unclear etiologies and there is no standardized treatment protocol, but rather a condition-specific decision.
Definition
Interstitial lung disease is a general term for a group of diffuse lung diseases that primarily involve the interstitial and alveolar spaces of the lungs and result in the loss of alveolar-capillary functional units.
In total, it includes more than 200 acute and chronic lung diseases, both common and rare, most of which have not yet had a clear etiology.
Classification
Based on etiology, clinical and pathologic features, the American Thoracic Society (ATS) and the European Respiratory Society (ERS) classified interstitial lung diseases into the following 4 categories in 2013:
Interstitial lung disease of known cause
These mainly include hypersensitivity pneumonitis caused by inhalation of organic dust, asbestosis and silicosis caused by inhalation of inorganic dust, and pulmonary fibrosis caused by drugs or connective tissue diseases.
Idiopathic interstitial pneumonia (IIPS)
Idiopathic interstitial pneumonias are a group of interstitial pneumonias of unknown etiology, which can be subdivided into three categories according to whether they are clinically common or not: major interstitial pneumonias, rare interstitial pneumonias, and interstitial pneumonias that fail to be classified.
Granulomatous interstitial lung diseases
This mainly includes nodular disease, etc.
Rare interstitial lung diseases
Including pulmonary lymphangioleolar smooth muscle disease, alveolar protein deposition disease, alveolar microlithiasis, pulmonary amyloidosis, etc.
Incidence
The incidence of interstitial lung diseases is showing a significant increase in China.
Age-wise, the incidence of interstitial lung diseases is dominated by middle-aged and elderly people over 50 years old.
The most common diseases in men include idiopathic interstitial pneumonia and diffuse panuberculous bronchitis. In women, the most common diseases include cryptogenic mechanized pneumonia, non-specific interstitial pneumonia, and nodular disease.
Occupationally, a larger proportion of patients with interstitial lung disease have a clear occupational history, with farmers, dust environment workers, cotton textile industry, etc. predominating.
Causes
Causes
Interstitial lung diseases comprise more than 200 conditions, most of which have an unknown specific etiology.
The largest group of known causes are occupational and environmental inhalation diseases, including inhalation of inorganic dusts, organic dusts, and various irritating toxic gases.
Antibiotics (e.g., furotoxin, azoxystrobin salicylate), cardiovascular drugs (e.g., amiodarone), antineoplastic drugs (e.g., bleomycin, methotrexate), and other chemicals (e.g., paraquat, penicillin, etc.) can also contribute to the development of the disease.
High risk factors
As interstitial lung disease is a large group of diseases, risk factors vary from disease to disease.
Poor working and living environments and prolonged exposure to specific dusts, gases and compounds are more likely to lead to the development of interstitial lung disease.
Long-term abuse of medications such as amiodarone, bleomycin, and methotrexate, as well as radiation therapy, also increase the likelihood of developing the disease.
Patients who have their own connective tissue diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.) or vasculitis are more likely to contribute to the development of interstitial lung disease.
Smoking is also an important factor in the development of interstitial lung disease, and respiratory bronchiolitis with interstitial lung disease (RBILD) occurs almost exclusively in smokers.
Pathogenesis
The pathogenesis of different interstitial lung diseases differs markedly, and the mechanisms of how they ultimately lead to pulmonary fibrosis have not been fully elucidated. However, there is a common pattern of inflammation of the interstitium, alveoli, pulmonary capillaries, or terminal airways during the pathogenesis of interstitial lung disease, which leads to the formation of pulmonary fibrosis during the process of inflammatory damage and repair.
Symptoms
Main Symptoms
The clinical manifestations of different interstitial lung diseases are not exactly the same, most of them start insidiously, and the most common symptoms are dyspnea and cough.
Dyspnea
Dyspnea is characterized by progressively worsening breathlessness (shortness of breath).
In the early stages of the disease, dyspnea usually occurs only after more strenuous activity and worsens progressively as the disease progresses.
Cough
A dry cough is also a common symptom of interstitial lung disease and is usually persistent.
Other symptoms
Hemoptysis, chest pain and wheezing are rare.
Cyanosis may be present in 23% to 53% of patients, indicating advanced disease.
If the patient has connective tissue disease, there may also be fever, night sweats, malaise, lethargy, swelling and deformity of the joints, and skin rashes.
Complications
Lung infections
As glucocorticosteroids and immunosuppressants are often used in the treatment of interstitial lung diseases, the incidence of lung infections will be increased to a certain extent, resulting in lung infections becoming one of the most common complications of interstitial lung diseases.
It can be manifested as cough, sputum, fever and chest pain.
Spontaneous pneumothorax
The alveoli of patients with interstitial lung disease are usually highly inflated, causing the walls of the alveoli to thin, rupture, and fuse with each other to form large, space-occupying pulmonary blisters. In this case, sudden exertion, violent coughing and other stimuli that rupture the blisters can lead to spontaneous pneumothorax.
It may be manifested as chest tightness, chest pain and dyspnea.
Interstitial lung disease
Patients with interstitial lung disease often suffer from chronic hypoxia and progressive pulmonary hypertension because of progressive dyspnea. If not treated aggressively, it can lead to increased right ventricular loading and right ventricular hypertrophy, triggering pulmonary heart disease.
This may be manifested by decreased labor endurance after activity, fatigue, palpitations, and dyspnea.
Consultation
Department of Medicine
Respiratory Medicine
If dyspnea, shortness of breath and fatigue worsen progressively, it is recommended to consult a respiratory physician promptly.
Preparation
Preparation for consultation: registration, preparation of documents, common problems
Tips for medical treatment
Careful recording of the time of onset and change of symptoms may help in the diagnosis of the disease.
Preparation Checklist
Symptom list
Pay particular attention to the time of onset of symptoms and specific manifestations.
Are there any symptoms of dyspnea or shortness of breath?
Is there a cough? Is there sputum? What kind of phlegm?
Are there hot flashes, night sweats, swelling of muscles and joints?
When did these symptoms start?
Are there any factors that could trigger exacerbation or remission?
Medical History Checklist
Is there any family history of rheumatoid arthritis or systemic lupus erythematosus?
What medications have you taken recently?
What kind of occupation do you usually work in? Is there any exposure to dust?
Are there any other lung diseases? Or heart disease, connective tissue disease?
Is there any smoking?
Checklist
Test results from the last six months, which can be brought to the doctor’s office
Imaging tests: Chest CT, chest X-ray.
Specialized tests: pulmonary function test result report.
Medication List
Medication used in the last 3 months, if available in boxes or packages, can be brought to the doctor’s office
Amiodarone, bleomycin, methotrexate, etc.
Diagnosis
Diagnosis based on
medical history
Presence of symptoms such as dyspnea or cough that are progressively worse.
Taking medications that can cause pulmonary fibrosis, such as amiodarone and methotrexate.
History of specific occupations that expose you to dust.
History of long-term smoking.
Clinical manifestations
Symptoms
Progressive dyspnea and cough, occasionally hemoptysis and chest pain.
Others may include lethargy, fatigue, and loss of appetite.
Skin rash and swollen and deformed joints may suggest connective tissue disease.
Physical signs
In most patients with interstitial lung disease, small end-inspiratory crackles or Velcro rales may be detected on auscultation at the base of both lungs.
Some patients with idiopathic interstitial pneumonitis may also develop pestle and mortar fingers, which are an early indication of severe disease.
Laboratory tests
Laboratory tests in patients with interstitial lung disease are usually nonspecific, but routine blood tests, blood biochemistry, liver and renal function, and erythrocyte sedimentation rate (ESR) are needed to indicate the cause of the interstitial lung disease or concomitant diseases.
Eosinophilia is seen in eosinophilic pneumonia, and an increase in angiotensin-converting enzyme supports the diagnosis of nodular disease.
Immunologically relevant screening indices-such as antinuclear antibodies, anti-extractable nuclear antigen antibody (ENA) antibody profile, anti-double-stranded DNA antibodies, anti-neutrophil cytoplasmic antibodies (ANCA), and rheumatoid factor (RF)-can help determine the presence of connective tissue disease.
Lung function tests
Lung function tests mainly include ventilation function tests and air exchange function tests.
Ventilation Function Test
It can understand the lung volume of the patient and clarify whether there is any obstacle in the ventilation function of the lungs.
The main indicators include total lung volume (TLC), lung capacity (VC), residual volume of air (RV), etc. A decrease in these indicators suggests that the patient’s ventilation is impaired. In addition, the patient’s first-second expiratory volume/expiratory lung capacity (FEV1/FVC) is usually normal or increased.
Ventilatory function tests
This test provides information on the distribution of inhaled gases in the lungs and blood flow status.
The main indicators are diffusion volume of carbon monoxide (DLco), etc. Decrease in this indicator, or hypoxemia, suggests that the patient has a ventilation dysfunction.
Imaging
X-ray
Most patients with interstitial lung disease have diffuse infiltrative shadows on chest X-ray, but a normal chest X-ray cannot exclude the possibility of interstitial lung disease.
High-resolution CT of the chest
High-resolution CT of the chest can show the extent and nature of lung parenchymal abnormalities in greater detail and assist in diagnosis.
Patients with interstitial lung disease usually have diffuse nodular shadows, ground-glass lesions, alveolar parenchyma, interlobular septal thickening, subpleural lines, latticework with cystic cavities, or honeycomb changes, often accompanied by stretched bronchiolar dilatation or structural changes in the lungs.
Fiberoptic bronchoscopy
Bronchoalveolar lavage and/or transbronchial lung biopsy may be performed to characterize diffuse pulmonary exudative lesions and to assist in identifying interstitial lung disease.
Pathologic examination
For interstitial lung diseases that cannot be definitively diagnosed based on clinical symptomatology, high-resolution CT features of the chest, or even bronchopulmonary biopsy and bronchoalveolar lavage, surgical lung biopsy is required to clarify the pathologic changes and diagnosis.
Diagnostic criteria
The clinical diagnosis of a particular interstitial lung disease is a dynamic process that requires close collaboration between clinical, radiologic, and pathologic physicians to validate or revise the previous diagnosis based on the complete information obtained.
Clinicians need to make a preliminary diagnosis by taking into account the patient’s clinical presentation, physical examination findings, imaging findings, pulmonary ventilation and diffusion function, endoscopic findings, and pathologic findings, and to exclude other known causes of interstitial lung disease.
Differential Diagnosis
Differential diagnosis of interstitial lung disease is primarily a diagnosis of the type of disease.
Different types of interstitial lung diseases usually do not have the same triggers, which can be used as the basis for differential diagnosis. For example, allergic pneumonitis usually has a clear history of exposure to organic dust antigens, and asbestosis, silicosis, etc. have a clear history of exposure to inorganic dust.
In addition, characteristic pathologic changes are also important in supporting the diagnosis. For example, common type interstitial pneumonia is a characteristic pathological change of idiopathic pulmonary fibrosis, which can be used as the gold standard for diagnosis. However, at the same time, common type interstitial pneumonia can also be seen in chronic hypersensitivity pneumonitis, asbestosis and other diseases, so other factors need to be excluded in the diagnosis.
The differentiation of interstitial lung disease requires a comprehensive evaluation of the patient’s medical history, pathologic features and other factors before making a diagnosis.
Treatment
Aims of treatment: to reduce the inflammatory response and to stop or reduce the development of pulmonary fibrosis.
Treatment principle: There are many types of interstitial lung diseases, and the treatment plan for each disease is different, and there is no uniform treatment plan. There is no standardized treatment plan, and even for different patients with the same disease, the treatment plan will be adjusted according to the cause of the disease and the individual’s physical condition. Therefore, the current treatment plans are individualized and precise.
General Treatment
When there are known triggering factors that can cause or aggravate the condition, the first step in treatment should be to avoid or detach from the known triggering factors.
Oxygen may be administered for hypoxemia.
Pneumococcal and influenza vaccines should be administered to all patients diagnosed with interstitial lung disease, except where contraindicated.
Asymptomatic and normal lung function Stage I nodular disease, and asymptomatic and stable Stage II and III with mildly abnormal lung function do not require treatment.
Medication
The treatment of interstitial lung disease is based on glucocorticoids because the etiology and pathogenesis of most interstitial lung diseases are unclear, and glucocorticoids can reduce the inflammatory response, thus stopping or reducing the progression of pulmonary fibrosis. Commonly used drugs include prednisone and methylprednisolone.
For some chronic fibrotic lung diseases with relatively poor prognosis, single glucocorticoid therapy or combination of other immunosuppressants (azathioprine, cyclophosphamide, etc.) can be applied for treatment.
In patients with idiopathic pulmonary fibrosis, treatment with pirfenidone or nidanib slows the decline in lung function.
For patients with progressive pulmonary fibrosis (i.e., patients with interstitial lung disease who have experienced at least 2 of the following 3 criteria within the past year: worsening of respiratory symptoms, physiologic evidence of disease progression, and imaging evidence of disease progression), treatment with nidazanib may be used if it fails after standard therapy.
Other treatments
Whole-lung lavage is the preferred and effective treatment for patients with alveolar proteinosis who have significant respiratory dysfunction.
In patients with recalcitrant and severe alveolar hemorrhagic syndrome, plasma exchange may be applied if treatment with glucocorticoids and immunosuppressive agents is not effective.
Lung transplantation may be applied after a strict evaluation of indications and contraindications in those who do not respond well to current therapies.
Prognosis
Cure
The prognosis of interstitial lung disease is related to the specific disease and to the different conditions, with both disease and individual differences.
Acute and granulomatous interstitial lung disease usually recovers after removal of allergens and corticosteroid therapy, and chronic eosinophilic pneumonitis has a more satisfactory outcome with corticosteroid therapy.
The prognosis of nodular disease with acute onset is better with treatment or spontaneous remission, while chronic progressive nodular disease, especially with multiple organ function damage and extensive pulmonary fibrosis, has a poorer prognosis, with an overall case fatality rate of 1% to 5%.
The natural course and outcome of idiopathic pulmonary fibrosis varies widely among individuals, with a median survival of 2 to 3 years.
Chronic fibrotic lung diseases have a relatively poor prognosis.
Hazards
Interstitial lung disease can jeopardize the respiratory system and even involve organs such as the heart, which can be life-threatening in severe cases.
Patients with interstitial lung diseases will have progressive dyspnea, which affects the quality of life of patients to a great extent.
Daily
Daily management
Stop smoking and drinking.
Attention should be paid to balanced nutrition, and more food with high protein, high calories and high vitamins should be eaten, such as poultry, meat, eggs, vegetables and fruits.
Attention should be paid to room ventilation, and home oxygen therapy can be used if possible.
Normally, you can do appropriate exercise, chest expansion or deep breathing, etc., to enhance lung function.
Family members should care more about the patient and help the patient to overcome the disease, so as to avoid anxiety, depression, fear and other negative psychology due to long-term and continuous dyspnea.
Disease monitoring
In daily life, family members should pay attention to the color of the patient’s lips and mouth, whether edema occurs, and the amount of urine. Once the patient has cyanosis, edema of the lower limbs or face, and low urine output, etc., the patient should be sent to the doctor for treatment.
Prevention
There are no effective measures to avoid interstitial lung disease completely. It is recommended to stay away from dusty environments in daily life or keep wearing protective masks. People with a history of smoking are advised to quit smoking and avoid second-hand smoke. Regular medical checkups are recommended for early detection and treatment.