Pneumoconiosis

Pneumoconiosis is an occupational disease that results from the inhalation and deposition of mineral dusts and other inorganic particles in the lung. It can be categorized according to the type of causative particle involved or by the type of response provoked. Coal, silica, asbestos, and talc are the classic fibrogenic types, while beryllium provokes a granulomatous response, and cobalt is associated with giant cell pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia. Iron, tin, and barium are considered benign or inert particle types because they do not cause the same type of reactions as the others.
After exposure to the fibrogenic types of particles, macrophages and fibroblasts become activated within the pulmonary parenchyma leading to chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and fibrosis, which can progress to respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure and death. Occupational history and chest X-rays X-rays X-rays are high-energy particles of electromagnetic radiation used in the medical field for the generation of anatomical images. X-rays are projected through the body of a patient and onto a film, and this technique is called conventional or projectional radiography. X-rays are the mainstays of diagnosis and staging Staging Cancer is the 2nd leading cause of death in the US after cardiovascular disease. Many malignancies are treatable or curable, but some may recur. Thus, all malignancies must be assigned a grade and stage in order to guide management and determine prognosis. Grading, Staging, and Metastasis. Management is mainly symptomatic.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Epidemiology and Etiology

Definition and types

Pneumoconiosis is the classic term used to describe the non-neoplastic lung reaction to chronic inhalation of mineral dusts encountered at the workplace. Some lung experts believe that the term “pneumoconiosis” should also include diseases induced by chemical fumes and vapors but this is not a widespread practice and will not be followed here.

Most common causes:

  • Silicosis: caused by crystalline silica dust (< 5 microns)
  • Asbestosis: caused by asbestos fibers (crystalline hydrated silicates) < 10 microns
  • Coal worker’s pneumoconiosis (CWP) or anthracosis: caused by coal dust
  • Berylliosis: also called  chronic beryllium disease, caused by beryllium (alkali earth metal, lighter than aluminum, stronger than steel) 

Less common causes, not discussed further in this monograph:

  • Siderosis: caused by iron oxide, seen in welders
  • Stannosis: caused by tin oxide, affects workers who mine it
  • Baritosis: caused by barium sulfate, affects workers who mine it
  • Hard metal pneumoconiosis:
    • Caused by cobalt with or without tungsten carbide
    • Affecting workers who process it and diamond polishers
  • Talcosis:
    • Caused by talc powder, which is composed of crystalline hydrous magnesium silicate
    • Affects workers in industries that make or process ceramics, paper, plastics, rubber, paint, and cosmetics

Epidemiology

  • Silicosis:
    • Most common form of occupational lung disease
    • Currently, > 2 million workers are exposed to silica dust worldwide.
    • In 2016, the Global Burden of Disease Study estimated 10,400 deaths per year, and 210,000 years of life lost due to silicosis.
    • Incidence and mortality have decreased in the past several decades due to better workplace protection and regulations. 
  • Asbestosis:
    • 150,000 cases and 3,600 deaths in 2015
    • Exposure has greatly decreased due to the enforcement of environmental rules and regulations.
    • Asbestos is the most commonly encountered carcinogen.
  • CWP:
    • Common condition among coal miners
    • Estimated prevalence of 30% 
  • Berylliosis:
    • Rare form of pneumoconiosis
    • Overall prevalence among exposed workers ranges from 1%5% 

Risk factors

  • Silicosis:
    • Occupational: mining, sandblasting, quarry, ceramics, and foundry workers; and in grinding, stone cutting, fiberglass, and glass manufacturing
  • Asbestosis
    • Occupational: shipbuilding, roofing, plumbing, and demolition
    • Nonoccupational: family members of exposed workers, geological sources, smoking (accelerates disease progression)
  • CWP: coal miners
  • Berylliosis
    • Occupational: aerospace, ceramics, and metallurgical industries; electronics repair; jewelry makers; and dentists
    • Nonoccupational: family members of workers, or those living 5 miles or less from a beryllium manufacturing facility 

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Pathophysiology

  1. Inhaled toxic fibers cannot be metabolized by the body and accumulate in the alveolar ducts.
    • The most dangerous particles measure 1 to 5 µm, since they are able to be transported all the way into the terminal small airways and air sacs and settle there, provoking inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and fibrosis.
    • Asbestos occurs in two distinct geometric forms, 90% as curled serpentine forms like chrysotiles and 10% as needle-like amphibole forms.
    • Amphibole asbestos fibers are more pathogenic (especially for the development of mesothelioma Mesothelioma Malignant mesothelioma (usually referred to as simply "mesothelioma") is the malignant growth of mesothelial cells, most commonly affecting the pleura. The majority of cases are associated with occupational exposure to asbestos that occurred > 20 years before clinical onset, which includes dyspnea, chest pain, coughing, fatigue, and weight loss. Malignant Mesothelioma) than chrysotiles because they can travel farther and penetrate deeper into tissues.
  2. The fibers are engulfed by macrophages, which undergo lysis and release cytokines.
  3. Cytokines induce an inflammatory reaction, producing airway obstruction Airway obstruction Airway obstruction is a partial or complete blockage of the airways that impedes airflow. An airway obstruction can be classified as upper, central, or lower depending on location. Lower airway obstruction (LAO) is usually a manifestation of chronic disease, such as asthma or chronic obstructive pulmonary disease (COPD). Airway Obstruction and stimulating fibroblasts.
  4. Fibrotic scarring leads to thickening of the airways, reduced elasticity, and impaired gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange.

Fiber-specific pathogenesis:

  • Progressive massive fibrosis (PMF)  
    • Can occur in both silicosis and CWP
    • Represents an evolution from the simple form of pneumoconiosis with small nodules to the complicated form when the nodules coalesce to form larger nodules that can evolve into PMF
  • Asbestosis affects the lower lobes first and the pleura Pleura The pleura is a serous membrane that lines the walls of the thoracic cavity and the surface of the lungs. This structure of mesodermal origin covers both lungs, the mediastinum, the thoracic surface of the diaphragm, and the inner part of the thoracic cage. The pleura is divided into a visceral pleura and parietal pleura. Pleura (unusual in other interstitial lung disorders)
  • Silicosis, CWP, and berylliosis affect the upper lobes first.
  • Berylliosis leads to the development of noncaseating granulomas (delayed hypersensitivity reaction)
    • Direct contact with beryllium fumes or dusts may injure the exposed areas of the body, such as the eyes or the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin, and sensitization may occur

Factors of disease progression:

  • Size, type, and physiochemical reactivity of inhaled fibers 
  • Duration of exposure (disease may continue to progress even after the end of exposure) 
  • Intensity of exposure (dose-response relationship)
  • Genetic susceptibility of the individual is likely since only a small percentage of exposed people develop occupational exposure respiratory diseases: Mutations of the HLA-DPB1 gene produce a higher susceptibility to beryllium.
  • Smoking habits and exposure to other toxins/pollutants

Clinical Presentation

General signs and symptoms

  • Progressive exertional dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
  • Dry cough
    • May be productive in the morning, with clear-to-white sputum, or yellow, purulent, in the case of concomitant bacterial pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Rare in cases of asbestosis in the absence of concomitant cigarette smoking
  • Inspiratory rales or crackles
  • Digital clubbing in advanced disease
  • Berylliosis also presents less commonly with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain, arthralgias, weight loss, and nodules on the areas of exposed skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin.

Onset

Onset depends on the intensity and duration of exposure and of the type of dust inhaled.

  • Silicosis usually presents after > 10 years of exposure but can manifest after several months of intense daily exposure.
  • Asbestosis presents after > 20 years of exposure.
  • CWP presents after prolonged exposure (> 10 years).
  • Berylliosis presents within weeks to decades after initial exposure. The rate of progression from sensitization to disease may vary from 6%8%.

Complications

  • Tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis (increased risk in silicosis) 
  • Bronchogenic carcinoma (most common neoplastic complication) 
    • Develops > 15 years after exposure
    • Increased amount of exposure is associated with a higher risk of lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer 
  • Mesothelioma (especially with asbestosis)
    • Can develop as early as 12 years after intense asbestos exposure or later, up to 40 years after exposure
  • Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension, cor pulmonale Cor Pulmonale Cor pulmonale is right ventricular (RV) dysfunction caused by lung disease that results in pulmonary artery hypertension. The most common cause of cor pulmonale is chronic obstructive pulmonary disease. Dyspnea is the usual presenting symptom. Cor Pulmonale, respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure, and right-sided heart failure 
  • Caplan’s syndrome (a type of pneumoconiosis with intrapulmonary nodules in combination with rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis)

Diagnosis

A diagnosis of occupational lung disease relies upon 4 essential criteria:

  1. Documented exposure history to a known toxic agent
  2. A typical latent period between exposure and symptoms
  3. Clinicoradiological features compatible with the known features of the disease
  4. Exclusion of any other disease that could explain the findings

Chest X-ray

Silicosis Asbestosis CWP Berylliosis
  • Multiple small nodules, generally in the upper lobes
  • Diffuse ground-glass opacities in perihilar and basilar regions
  • Eggshell-like calcifications in marginal lymph node sinuses of hilar lymph nodes (can also be seen in CWP, sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis, treated lymphoma)
  • “Ivory-white,” calcified, supradiaphragmatic, and pleural plaques
  • Interstitial fibrosis as linear streaking or honeycomb changes
  • Simple CWP: lung nodules < 1 cm in diameter in the upper lung lobes
  • Progressive (complicated) disease: multiple small nodules and 1 large nodule (> 1 cm)
  • Early findings: normal
  • Later findings: interstitial fibrosis, pleural irregularities, ground-glass opacities, and hilar lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy

Pulmonary function tests

Most cases of pneumoconiosis show a restrictive lung disease pattern by spirometry.

  • ↓ functional vital capacity (FVC) and total lung capacity
  • ↓ diffusion capacity (DLCO)
  • Normal forced expiratory volume in 1 second (FEV1)/FVC ratio (may be decreased if the patient is also a smoker = mixed restrictive and obstructive lung disease)

Laboratory tests

  • Usually not helpful in the confirmation of the diagnosis but can exclude infectious complications
  • Beryllium lymphocyte proliferation test (BePLT): test of choice to diagnose beryllium sensitization or berylliosis
    • Mononuclear cells from the patient (from blood or obtained by bronchoalveolar lavage) exposed to different concentrations of beryllium salts  
    • Increased lymphocyte proliferation is a positive result.

Confirmatory tests

  • High-resolution computed tomography
  • Bronchoscopy with bronchoalveolar lavage (BAL):  to exclude infection or malignancy
  • Video-assisted transthoracic or open biopsy:
    • Gold standard for diagnosis but rarely needed; should be limited to exclude malignancy or when there is no known history of exposure to mineral dust
    • Silicosis shows nodules with silica particles usually in a central hyalinized region surrounded by concentric collagen fibers.
    • Asbestosis may rarely show asbestos bodies that stain positive with Prussian blue and appear as dumbbell-shaped and golden-brown fusiform rods.
    • CWP shows 1–2 mm nodular aggregations of anthracotic macrophages supported by a fine collagen network in the upper regions of the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs around respiratory bronchioles.
    • Berylliosis shows noncaseating granulomas and/or mononuclear cell interstitial infiltrates.

Management

  • There is no definitive treatment for pneumoconiosis, regardless of the clinical stage.
  • Immediate cessation of exposure is recommended as well as cessation of tobacco smoking habits, if applicable.
    • Stopping exposure may not stop the progression of the disease.
  • Management is largely supportive and focuses on the prevention of further progression and complications. 
    • Prophylactic vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination against influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza and pneumococcal pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • If there is evidence of underlying obstructive disease, bronchodilator therapy can be administered.
    • Oxygen therapy is often necessary to relieve dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea.
    • Early systemic oral glucocorticoid therapy may relieve symptoms, improve lung appearance on imaging, and normalize pulmonary function testing scores.
    • Immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants, (e.g., methotrexate, azathioprine) are an option for patients who are refractory to glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids, or those experiencing adverse effects.
  • Lung transplantation has been performed for advanced pneumoconiosis with respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure, but evidence on patient outcomes is lacking. 
  • Pulmonary rehabilitation can improve quality of life; includes patient education, exercise/breathing training, nutrition advice, and psychosocial support.

Differential Diagnosis

The differential diagnoses of pneumoconioses caused by mineral dusts include the following conditions:

  • Idiopathic pulmonary fibrosis Pulmonary Fibrosis Idiopathic pulmonary fibrosis is a specific entity of the major idiopathic interstitial pneumonia classification of interstitial lung diseases. As implied by the name, the exact causes are poorly understood. Patients often present in the moderate to advanced stage with progressive dyspnea and nonproductive cough. Pulmonary Fibrosis: most common interstitial lung disease, characterized by irreversible pulmonary fibrosis Pulmonary Fibrosis Idiopathic pulmonary fibrosis is a specific entity of the major idiopathic interstitial pneumonia classification of interstitial lung diseases. As implied by the name, the exact causes are poorly understood. Patients often present in the moderate to advanced stage with progressive dyspnea and nonproductive cough. Pulmonary Fibrosis and impaired pulmonary function. Presents with exertional dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, persistent dry cough, and fatigue
  • Hypersensitivity pneumonitis Hypersensitivity Pneumonitis Hypersensitivity pneumonitis (HP), previously called extrinsic allergic alveolitis, is an immunologically induced inflammatory disease affecting the alveoli, bronchioles, and lung parenchyma. It is caused by repeated inhalation of an inciting agent in a susceptible host that triggers first a type III (complement-mediated) hypersensitivity reaction in the acute phase and then a type IV (delayed) reaction in the subacute and chronic phases. Hypersensitivity Pneumonitis: pulmonary disease characterized by an immune-mediated inflammatory response in the small airways as a result of exposure to inhaled antigens
  • Sarcoidosis: chronic inflammatory disease characterized by the formation of noncaseating granulomas, typically in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs and, less commonly, the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, eyes, and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin
  • Tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis: disease caused by Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium tuberculosis. The bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview usually attack the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs, but can also damage other parts of the body.

References

  1. Stark, P. Imaging of occupational lung diseases. UpToDate Evidence-Based Medicine. Retrieved August 13, 2020, from https://www.uptodate.com/contents/imaging-of-occupational-lung-diseases?search=pneumoconiosis&source=search_result&selectedTitle=1~125&usage_type=default&display_rank=1#H365264570
  2. Rose, C. Silicosis. UpToDate Evidence-Based Medicine. Retrieved August 13, 2020, from https://www.uptodate.com/contents/silicosis?search=pneumoconiosis&source=search_result&selectedTitle=2~125&usage_type=default&display_rank=2
  3. King, T.E. Asbestos-related pleuropulmonary disease. UpToDate Evidence-Based Medicine. Retrieved August 13, 2020, from https://www.uptodate.com/contents/asbestos-related-pleuropulmonary-disease?search=pneumoconiosis&source=search_result&selectedTitle=3~125&usage_type=default&display_rank=3
  4. Hu, C. X., Chen, W. H., He at al. (2019). Lung transplantation in China between 2015 and 2018. Chinese medical journal, 132(23), 2783–2789. https://doi.org/10.1097/CM9.0000000000000543

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