Pneumoconiosis

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 Anthracosis A diffuse parenchymal lung disease caused by accumulation of inhaled carbon or coal dust. The disease can progress from asymptomatic anthracosis to massive lung fibrosis. This lung lesion usually occurs in coal miners, but can be seen in urban dwellers and tobacco smokers. Cellular Accumulations: 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 Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements oxide, seen in welders
• Stannosis: caused by tin oxide, affects workers who mine it
• Baritosis: caused by barium sulfate Barium sulfate A compound used as an x-ray contrast medium that occurs in nature as the mineral barite. It is also used in various manufacturing applications and mixed into heavy concrete to serve as a radiation shield. Computed Tomography (CT), 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 Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes 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 Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency and mortality Mortality All deaths reported in a given population. Measures of Health Status 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 Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of 30% 
• Berylliosis:
  • Rare form of pneumoconiosis
  • Overall prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency 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 Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases (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 

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 Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans.
   • 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 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, which undergo lysis and release cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response.
3. Cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response induce an inflammatory reaction, producing airway Airway ABCDE Assessment obstruction and stimulating fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis.
4. Fibrotic scarring Scarring Inflammation leads to thickening of the airways, reduced elasticity Elasticity Resistance and recovery from distortion of shape. Skeletal Muscle Contraction, 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 Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans (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: Anatomy (unusual in other interstitial lung disorders)
• Silicosis, CWP, and berylliosis affect the upper lobes first.
• Berylliosis leads to the development of noncaseating granulomas Noncaseating granulomas Crohn’s Disease ( delayed hypersensitivity reaction Delayed Hypersensitivity Reaction Glycopeptides)
  • 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. Skin: Structure and Functions, 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 Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics produce a higher susceptibility to beryllium.
• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases 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 Dry Cough Strongyloidiasis
  • 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 Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
• Inspiratory rales Rales Respiratory Syncytial Virus or crackles
• Digital clubbing Clubbing Cardiovascular Examination 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 Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, arthralgias, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, 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. Skin: Structure and Functions.

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 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 (especially with asbestosis)
  • Can develop as early as 1–2 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 Right-Sided Heart Failure Ebstein’s Anomaly 
• Caplan’s syndrome (a type of pneumoconiosis with intrapulmonary nodules in combination with rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis)

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 Latent period The time between onset of the AP and onset of the muscle contraction (i.e., the twitch) Skeletal Muscle Contraction 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 X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests

Pulmonary function tests

Most cases of pneumoconiosis show a restrictive lung disease pattern by spirometry Spirometry Measurement of volume of air inhaled or exhaled by the lung. Pulmonary Function Tests.

• ↓ functional vital capacity Vital capacity The volume of air that is exhaled by a maximal expiration following a maximal inspiration. Ventilation: Mechanics of Breathing (FVC) and total lung capacity Total lung capacity The volume of air contained in the lungs at the end of a maximal inspiration. It is the equivalent to each of the following sums: vital capacity plus residual volume; inspiratory capacity plus functional residual capacity; tidal volume plus inspiratory reserve volume plus functional residual capacity; or tidal volume plus inspiratory reserve volume plus expiratory reserve volume plus residual volume. Ventilation: Mechanics of Breathing
• ↓ diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis capacity (DL_CO)
• 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 Bronchoalveolar lavage Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. Pulmonary Fibrosis) exposed to different concentrations of beryllium salts  
  • Increased lymphocyte proliferation is a positive result.

Confirmatory tests

• High-resolution computed tomography
• Bronchoscopy Bronchoscopy Endoscopic examination, therapy or surgery of the bronchi. Laryngomalacia and Tracheomalacia with bronchoalveolar lavage Bronchoalveolar lavage Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. Pulmonary Fibrosis (BAL):  to exclude infection or malignancy Malignancy Hemothorax
• Video-assisted transthoracic or open biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
  • Gold standard for diagnosis but rarely needed; should be limited to exclude malignancy Malignancy Hemothorax 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 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology 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 MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma nodular aggregations of anthracotic macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation supported by a fine collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology 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: Anatomy around respiratory bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy.
  • Berylliosis shows noncaseating granulomas Noncaseating granulomas Crohn’s Disease 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 Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases 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 Pulmonary Function Testing Pulmonary Function Tests 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 Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy, azathioprine Azathioprine An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the fourth annual report on carcinogens, this substance has been listed as a known carcinogen. Immunosuppressants) are an option for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 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 Lung transplantation The transference of either one or both of the lungs from one human or animal to another. Organ 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 Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement 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 Idiopathic Dermatomyositis pulmonary fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans: most common interstitial lung disease, characterized by irreversible pulmonary fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans 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 Dry Cough Strongyloidiasis, and fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
• Hypersensitivity pneumonitis Pneumonitis Human Herpesvirus 6 and 7: pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis characterized by an immune-mediated inflammatory response in the small airways as a result of exposure to inhaled antigens
• 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: chronic inflammatory disease characterized by the formation of noncaseating granulomas Noncaseating granulomas Crohn’s Disease, 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: Anatomy 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: Anatomy, 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. Skin: Structure and Functions. 
• 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 tuberculosis Mycobacterium 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. 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 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: Anatomy, but can also damage other parts of the body.