Occupational lung disease

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Occupational lung diseases have long been described since the Egyptian and Roman empires existed. Dr. Benardino Ramazzini, described as the “father of occupational medicine” was first to coin the term “disease of workers” in the 17th century. Occupational lung disease may be classified according to the type of inhalant into 3 groups: inorganic dust, organic dust, and agents other than inorganic and organic dust.As the particles accumulate, the body’s elimination mechanisms begin to fail, resulting in activation of chemotactic factors that exacerbate the inflammatory response, and subsequently lead to fibrosis. Occupational lung disease may be caused by organic dust such as thermophilic and true fungi, and bacteria and animal proteins, or by inorganic dust such as, silicates, carbons and metals, or by agents other than organic or inorganic dusts such as, chemicals, gases, fumes, vapors and aerosols. Incidence, prevalence and mortality rates for occupational lung disease are not well documented and are unreliable. Disease manifestation is correlated to the frequency, duration and dose of inhalational exposure. Occupational lung disease has no predilection to race or gender, however, males tend to work in environments where exposure is common, therefore more males suffer from occupational lung disease. Occupational lung disease, particularly, coal worker’s pneumoconiosis is a common disease that tends to affect coal miners in West Virginia and Kentucky, USA and South Wales, UK. Common risk factors in the development of occupational lung disease include smoking, genetic susceptibility, cardiovascular disease, and frequency, intensity and duration of exposure. If left untreated, patients with occupational lung disease may progress to develop pleural effusion, interstitial lung fibrosis, and lung cancer. Common complications of of occupational lung disease include interstitial pulmonary fibrosis, progressive massive fibrosis, mesothelioma, and premature death. The initial study of choice for the diagnosis of occupational lung disease is a chest x-ray. The findings on x ray that are suggestive of occupational lung disease include, pleural thickening, plaques, calcifications, opacities and atelectasis. A positive history of occupational exposure to a particular agent with progressive worsening of respiratory symptoms including dyspnea, cough and fatigue. The most common symptoms of occupational lung disease include cough, shortness of breath, and wheezing. Physical examination of patients with occupational lung disease is usually remarkable for bronchial breathing, increased vocal resonance, and fine crepitations. A chest x-ray is the cornerstone of diagnosis in occupational lung disease. Findings on an x-ray suggestive of occupational lung disease include pleural thickening, pleural plaques, pleural abnormalities, calcification, small or large opacities, costophrenic angle obliteration, atelectasis, pneumothorax, parenchymal bands, enlarged hilar or mediastinal lymph nodes, bullae and granulomata. A high resolution chest CT scan or “thin-section” CT may be helpful in the further diagnosis of occupational lung disease. Findings on CT scan suggestive of occupational lung disease include nodules with sharp margination, opacities, lymph node hyperplasia and egg shell calcification, and interlobular septal thickening and intralobular lines. The mainstay of treatment for occupational lung disease is medical therapy. Surgery is usually reserved for patients with progressive massive fibrosis or lung cancer. Effective measures for the primary prevention of occupational lung disease include the prevention of smoking and smoking cessation, health awareness, and routine surveillance. Certain materials have been abolished from use in industry such as asbestos. Also reducing exposure through the use of medical masks and respirators, robots, isolation of harmful processes, ventilation, limiting exposure hours, maintenance of dust control systems, and the use of warning signs.

Occupational lung diseases have long been described since the Egyptian and Roman empires existed. The 10th century to the 18th century demonstrated the largest period of industrial mechanization and infrastructure, this led to the awareness and advent of occupational health hazards and sciences. These movements led to the rising need for trade unions and workers’ legislation. Dr. Benardino Ramazzini, described as the “father of occupational medicine” was first to coin the term “disease of workers” in the 17th century. Later in the 20th century , Dr. Alison Hamilton became a leading expert in occupational health.

Occupational lung disease may be classified according to the type of inhalant into 3 groups: inorganic dust, organic dust, and agents other than inorganic and organic dust.

Occupational lung diseases include the pneumoconioses (interstitial lung diseases), hypersensitivity pneumonitis, bronchiolitis, byssinosis, and occupational asthma. Pneumoconiosis is an interstitial lung disease caused by the accumulation of different dust particles in the alveolar space. As the particles accumulate, the body’s elimination mechanisms begin to fail, resulting in activation of chemotactic factors that exacerbate the inflammatory response, and subsequently lead to fibrosis. Hypersensitivity pneumonitis or extrinsic allergic alveolitis and its subcategories of, bronchiolitis, bysinnosis and occupational asthma are all part of the respiratory systems’ over reactivity towards inhalants.

Occupational lung disease may be caused by organic dust such as thermophilic and true fungi, and bacteria and animal proteins, or by inorganic dust such as, silicates, carbons and metals, or by agents other than organic or inorganic dusts such as, chemicals, gases, fumes, vapors and aerosols.

Occupational lung disease must be differentiated from other diseases that cause shortness of breath, cough, and wheeze, such as allergic asthma, emphysema, sarcoidosis, tuberculosis, and chronic bronchitis.

Incidence, prevalence and mortality rates for occupational lung disease are not well documented and are unreliable. Individual occupational lung diseases have separate prevalence and incidence rates, such as, farmer’s lung has an incidence of 270 cases per 100,000 in 2012. Whilst the mortality rates for work-related disease are approximately 63,000 deaths in 2012. Disease manifestation is correlated to the frequency, duration and dose of inhalational exposure. Occupational lung disease has no predilection to race or gender, however, males tend to work in environments where exposure is common, therefore more males suffer from occupational lung disease. Occupational lung disease, particularly, coal worker’s pneumoconiosis is a common disease that tends to affect coal miners in West Virginia and Kentucky, USA and South Wales, UK.

Common risk factors in the development of occupational lung disease include smoking, genetic susceptibility, cardiovascular disease, and frequency, intensity and duration of exposure.

There is insufficient evidence to recommend routine screening for occupational lung disease at a national level, however, at a local level workers with known occupational hazards benefit from a routine screening at their places of work.

If left untreated, patients with occupational lung disease may progress to develop pleural effusion, interstitial lung fibrosis, and lung cancer. Common complications of of occupational lung disease include interstitial pulmonary fibrosis, progressive massive fibrosis, mesothelioma, and premature death. Depending on the extent of the disease progression at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor.

The initial study of choice for the diagnosis of occupational lung disease is a chest x-ray. The findings on x ray that are suggestive of occupational lung disease include, pleural thickening, plaques, calcifications, opacities and atelectasis.

A positive history of occupational exposure to a particular agent with progressive worsening of respiratory symptoms including dyspnea, cough and fatigue. The most common symptoms of occupational lung disease include cough, shortness of breath, and wheezing. Less common symptoms of occupational lung disease include hemoptysis, weight loss, and loss of appetite.

Patients with occupational lung disease usually appear fatigued and short of breath. Physical examination of patients with occupational lung disease is usually remarkable for bronchial breathing, increased vocal resonance, and fine crepitations.

There are no diagnostic laboratory findings associated with occupational lung disease. However, useful laboratory findings consistent with the diagnosis of occupational lung disease include abnormal arterial blood gases, sputum analysis, and blood picture.

There are no ECG findings associated with occupational lung disease. However, chronic lung disease may be complicated by cor pulmonale. Findings on an ECG suggestive of cor pulmonale include, right axis deviation, R/S amplitude ratio in V1 greater than 1, R/S amplitude ratio in V6 less than 1, peaked P waves (P pulmonale in leads 2, 3, and aVF), S 1 Q 3 T 3 pattern and incomplete (or complete) right bundle branch block, and possibly, a low voltage QRS complex.

A chest x-ray is the cornerstone of diagnosis in occupational lung disease. Findings on an x-ray suggestive of occupational lung disease include pleural thickening, pleural plaques, pleural abnormalities, calcification, small or large opacities, costophrenic angle obliteration, atelectasis, pneumothorax, parenchymal bands, enlarged hilar or mediastinal lymph nodes, bullae and granulomata.

There are no echocardiography/ultrasound findings associated with occupational lung disease.

Initially, the first investigation recommended to diagnose occupational lung disease is a chest x-ray. A high resolution chest CT scan or “thin-section” CT may be helpful in the further diagnosis of occupational lung disease. Findings on CT scan suggestive of occupational lung disease include nodules with sharp margination, opacities, lymph node hyperplasia and egg shell calcification, and interlobular septal thickening and intralobular lines.

There are no MRI findings associated with occupational lung disease. However, a MRI may be helpful in distinguishing in (coal worker’s pneumonconiosis) progressive massive fibrosis from lung carcinoma.

PET may be helpful in the diagnosis and staging of mesothelioma. PET is also useful in distinguishing a fibrotic nodule from an actively inflamed nodule.

Other diagnostic studies for occupational lung disease include spirometry, which distinguishes obstructive from restrictive lung disease.

Supportive therapy for occupational lung disease before fibrotic disease sets in includes glucocorticoid therapy. Anti-asthmatic drugs may also be used to provide relief from dyspnea.

The mainstay of treatment for occupational lung disease is medical therapy. Surgery is usually reserved for patients with progressive massive fibrosis or lung cancer.

Effective measures for the primary prevention of occupational lung disease include the prevention of smoking and smoking cessation, health awareness, and routine surveillance. Certain materials have been abolished from use in industry such as asbestos. Also reducing exposure through the use of medical masks and respirators, robots, isolation of harmful processes, ventilation, limiting exposure hours, maintenance of dust control systems, and the use of warning signs.

Effective measures for the secondary prevention of occupational lung disease include cessation of smoking and exposure, and routine screening including skin prick tests, questionnaires and spirometry.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Occupational lung diseases have long been described since the Egyptian and Roman empires existed. The 10th century to the 18th century demonstrated the largest period of industrial mechanization and infrastructure, this led to the awareness and advent of occupational health hazards and sciences. These movements led to the rising need for trade unions and workers’ legislation. Dr. Benardino Ramazzini, described as the “father of occupational medicine” was first to coin the term “disease of workers” in the 17th century. Later in the 20th century , Dr. Alison Hamilton became a leading expert in occupational health.

• Occupational lung diseases have been described since the time of Egyptian, Grecian and Roman empires, where extensive land mining and building took place.^[1][2][3]
• Furthermore, in the 16th and 17th century an awareness for occupational health hazards became apparent with exposure to arsenic, lead and carbon monoxide.
• In the 18th century, Dr. Bernardino Ramazzini, described as “the father of occupational medicine” described the “disease of workers” in the 1700s.
• In the late 18th century, Hale introduced the importance of ventilation and Von Humboldt invented gas masks for coal workers.
• The advent of the industrial revolution beginning with cotton picking in India in the 10th century, and leading up to mechanization in Europe later in the 18th century greatly contributed to the prevalence of occupational lung disease.
• In the 19th century, workers that suffered from occupational disease initiated the legislation, trade union and insurance movements.
• In the 20th century, Dr. Alice Hamilton established the study on occupational disease, whilst Dr. Hariett Hardy and Dr. Irving Selikoff described berylliosis and asbestosis respectively.

• There has been a recent cluster discovery in February 2018 of coal worker’s pneumoconiosis amongst coal miner’s in Kentucky, Virginia and West Virginia.
• Coal worker’s pneumoconiosis complicated by progressive massive fibrosis in these regions was previously seen 5 – 7 times per year.
• As of February 2018, 154 new cases were diagnosed within one year.

• The slave trade and industrial revolution are crucial events in history that established many occupational hazards.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Occupational lung diseases include the pneumoconioses (interstitial lung diseases), hypersensitivity pneumonitis, bronchiolitis, byssinosis, and occupational asthma. Pneumoconiosis is an interstitial lung disease caused by the accumulation of different dust particles in the alveolar space. As the particles accumulate, the body’s elimination mechanisms begin to fail, resulting in activation of chemotactic factors that exacerbate the inflammatory response, and subsequently lead to fibrosis. Hypersensitivity pneumonitis or extrinsic allergic alveolitis and its subcategories of, bronchiolitis, byssinosis, and occupational asthma are all part of the respiratory systems’ over reactivity towards inhalants.

• The pathogenesis of pneumoconiosis starts with the inhalation of mineral, metallic, or dust particles.^[1][2][3][4]

• The most common particles that cause pneumoconiosis are:
  • Asbestos
  • Silica (quartz, cristobalite, coesite, or tridymite silica polymorphs)
    • Structural differences between the polymorphs of silica, are important because of the different degrees of biological reactivity they present, making some of them more toxic than others. The biological reactivity makes quartz more toxic, followed by tridymite, cristobalite, coesite, and finally stishovite.
  • Coal
  • Other dust particles may also lead to pneumoconiosis, such as hydrated magnesium silicate, hydrous aluminum silicate, bauxite, cobalt, beryllium, and iron.
• When particles reach the distal lung, the mucocilliary and lymphatic system take care of their elimination.
• Dust fibers must be less than 3 μm in diameter in order to penetrate the distal lung.
• Fibers greater than 5 μm are phagocytosed incompletely and retained in tissues.
• When particles increase in number, macrophages are activated to engulf those particles.
• Reticulin is then secreted by fibroblasts to entrap macrophages, as an attempt to control the excess of dust particles.
• The physiology of macrophage activation is subject to several theories:
  • The macrophages are mainly derived from peripheral blood monocytes and, from local replication.
  • The recruitment of monocytes from peripheral blood occurs in response to several chemotactic factors suggest that one of the most potent chemotactic factors for peripheral blood monocytes is monocyte chemoattractant protein – 1 (MCP – 1), suggesting its role in chronic macrophage inflammation.
  • TNFα activates MCP – 1 expression. MCP – 1 is a 76 amino acid peptide that activates monocytes, also increases its cytostatic activity, and the expression of monocyte adhesion molecules such as CD11c/CD18 and CD11b/CD18.
• As exposure continues, the elimination system begins to fail, leading to release of reactive oxygen species. These in turn exacerbate the inflammatory response, with the release of more cytokines, such as TNF and interleukins, which subsequently lead to fibrogenesis.
• In asbestosis, the macrophages cannot eliminate the fibers, and cause needle-like formations containing iron to coalesce, these bodies are known as asteroid bodies.
• In coal worker’s pneumoconiosis, coal dust trapped within the coalesced macrophages give a coal macule seen on x-ray.
• The determinants for the rate of disease progression are the accumulative dose; that is based on duration and intensity of exposure, the fiber type and individual susceptibility.
• The underlying pathogenic mechanisms that lead to pulmonary fibrosis in pneumoconiosis suggest a potential protective effect of TGF- β on the development of pulmonary fibrosis.
• The alveolar macrophages in coal miners with massive fibrosis, secretes two main profibrotic factors; platelet-derived growth factor (PDGF) and insulin-like growth factor 1 (IGF – 1), whereas, the patients with simple pneumoconiosis secretes transforming growth factor – β (TGF – β). This reinforces that TGF- β has a possible protective effect against the development of pulmonary fibrosis.

• Hypersensitivity is thought to develop via a two-hit hypothesis.^[1][5]
• Those with a genetic predisposition (no specific genes have been consistently associated) or a heavier than normal exposure will become sensitized.
• The second hit occurs with exposure to an antigen resulting in the manifestation of disease or its progression.
  • Individuals without an ability to suppress the expression of Th1 and Th2 cells via T regulatory cells are susceptible to a second hit.
• Acute hypersensitivity is thought to be a type III hypersensitivity reaction.
• Subacute and chronic hypersensitivity reactions are type IV hypersensitivity reactions.
  • CD4⁺ Th1 and Th17 cells are presented with antigens by dendritic cells and alveolar macrophages.
  • In response, an inflammatory cascade is triggered with the release of IFN ‒ γ, TNF, IL ‒ 17, and IL – 22.
  • The continuous presence of a numerous cytokines and chemokines causes mononuclear cells, macrophages, and fibroblasts to continually infiltrate the lung tissue.
  • Vast numbers of lymphocytes infiltrate the lung tissue intent on causing apoptosis, IL – 17 inhibits the lymphocytes from doing so.
  • As a result, this leads to the development of non-caseating granulomas and inflammation of the small airways, which is known as bronchiolitis.
  • In the chronic pattern of disease, a cytokine pattern lead primarily by CD4+ Th2 takes place, which is associated with the development of fibrosis in the lung.
  • Hallmarks for hypersensitivity pneumonitis include, cholesterol clefts, centrilobular fibrosis, peribronchiolar and bridging fibrosis.

• Each dust particle has a different degree of biological reactivity.^[3][4]
• This variability is due to properties in the surface of the particles.
• In the case of silica, there are two theories explaining their biological reactivity:
  • One theory states that silica is a hydrogen donor, whereas biological macromolecules are hydrogen acceptors, creating strong hydrogen bonds that contribute to the damage.
  • The second theory states that at a pH of 7.0, silica is negatively charged, and therefore attracts alveolar macrophages, and activates the generation of reactive oxygen species and cytokines.

Shown below is a table summarizing the dust exposure associated with pneumoconiosis:

Disease	Dust
Coal workers’ pneumoconiosis	Coal dust
Silicosis	Silica
Asbestosis	Asbestos
Talcosis	Hydrated magnesium silicate
Kaolin – induced pneumoconiosis	Hydrous aluminum silicate
Mixed dust pneumoconiosis	Coal dust, smoke from fires, and silicates
Aluminum – induced pneumoconiosis	Bauxite (Al2O3)
Berylliosis	Beryllium
Silicosiderosis	Silica and iron
Hard – metal disease (giant cell pneumonitis)	Cobalt

Conditions associated with occupational lung disease include:^[1]

• Asthma
• Chronic bronchitis
• Emphysema
• Allergic rhinitis
• Idiopathic pulmonary fibrosis
• Hives
• Eczema
• Mesothelioma
• Non-small cell lung cancer
• Tuberculosis
• Pleural effusion
• Pleural plaques and fibrosis
• Pulmonary edema

• Caplan syndrome is a rare complication of coal worker’s pneumoconiosis that occurs simultaneously with rheumatoid arthritis.^[6]

• In this syndrome, the joint manifestations of rheumatoid arthritis present with bilateral, peripheral lung nodules.
• These nodules are unique from other pneumoconiotic nodules in that they develop rapidly over a period of weeks and may form cavities or become calcified.

• On gross pathology, dilated airways, destruction and distortion of lung tissue, and discoloration of lung tissue are characteristic findings of occupational lung disease.^[7]

• On microscopic histopathological analysis, calcification, central necrosis, dense collagen, and sometimes malignant cells are characteristic findings of occupational lung disease.^[8]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Occupational lung disease may be classified according to the type of inhalant into 3 groups: inorganic dust, organic dust, and agents other than inorganic and organic dust.

• Occupational lung disease may be classified according to the type of inhalant into 3 groups:
  • Inorganic dust
    • Such as silicates, carbons, and metals
  • Organic dust
    • Thermophilic fungi, true fungi, bacteria and animal proteins
  • Agents that are neither organic or inorganic
    • Chemical sources, gases, vapors, fumes and aerosols

For a full classfication of occupational lung disease, please scroll down

Occupational lung disease

Organic dust

Inorganic dust

Agents other than organic or inorganic agents

Thermophilic and true fungi

Bacteria and animal proteins

Silicates

Carbons

Metals

Chemicals, gases, fumes, vapors and aerosols

• Farmer’s lung (Macropolyspora faeni) • Grain handler’s lung (Thermactinomyces vulgaris) • Humidifier or air conditioner lung (T. sacchari) • Aspergillus • Cryptostroma corticale • Aureobasidium pullulans • Penicillium species

• Bacillus subtilis • B. cereus • Bird fancier’s disease

• Silica (“silicosis”) • Asbestos (“asbestosis”) • Talc (hydrated Mg silicates; “talcosis”) • Kaolin or “china clay” (hydrated aluminum silicate) • Beryllium (“berylliosis”) • Mica (principally K and Mg aluminum silicates) • Portland cement • Aluminum silicates (sericite, sillimanite, zeolite) • Nepheline (hard rock containing mixed silicates) • Diatomaceous earth (Fuller’s earth, aluminum silicate with Fe and Mg)

• Coal dust (“coal worker’s pneumoconiosis”) • Graphite (“carbon pneumoconiosis”)

• Tin (“stannosis”) • Aluminum • Hard metal dusts (cadmium, tungsten, titanium and cobalt) • Iron (“siderosis”) • Antimony • Hematite (mixed dusts of iron oxide, silica and silicates; “siderosilicosis”) • Mixed dusts of silver and iron oxide (“argyrosiderosis”) • CuSO4 neutralized with hydrated lime (Bordeaux mixture; “vineyard sprayer’s lung”) • Rare earths (cerium, scandium, yttrium, lanthanum)

Chemical sources: • Synthetic – fiber lung (Orlon, polyesters, nylon, acrylic) • Bakelite worker’s lung pathways • Vinyl chloride, polyvinyl chloride powder Gases: • Oxygen • Oxides of nitrogen • Sulfur dioxide • Chlorine gas • Methyl isocyanate Fumes: • Oxides of zinc, copper, manganese, cadmium, iron, magnesium, nickel, brass, selenium, tin, and antimony • Diphenylmethane diisocyanate • Trimellitic anhydride toxicity Vapors: • Hydrocarbons • Thermosetting resins (rubber tire workers) • Toluene diisocyanate (TDI – asthmatic reactions prominent) • Oxygen • Mercury Aerosols: • Oils • Fats • Pyrethrum (a natural insecticide)

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Occupational lung disease may be caused by organic dust such as thermophilic and true fungi, and bacteria and animal proteins, or by inorganic dust such as, silicates, carbons and metals, or by agents other than organic or inorganic dusts such as, chemicals, gases, fumes, vapors, and aerosols.

• Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.
• Life-threatening causes of occupational lung disease include chemical gas inhalation such as chlorine or sarin gas.^[1][2]

Common causes of occupational lung disease include:^[3][4]

• Silica
• Asbestos
• Beryllium
• Mica
• Portland cement
• Aluminum silicates
• Aluminum
• Cadmium
• Tungsten
• Titanium
• Cobalt
• Iron
• Coal dust
• Graphite
• Macropolyspora faeni
• Thermactinomyces vulgaris
• Thermoactinomyces sacchari
• Aspergillus
• Copper sulfate neutralized with hydrated lime
• Bird droppings

Less common causes of occupational lung disease include:^[5][6]

• Vinyl chloride
• Oxygen
• Nitrogen oxide
• Sulfur dioxide
• Chlorine gas
• Methyl isocyanate
• Zinc
• Copper
• Manganese
• Cadmium
• Iron
• Magnesium
• Nickel
• Selenium
• Tin
• Antimony
• Diphenylmethane diisocyanate
• Trimellitic anhydride
• Hydrocarbons
• Thermosetting resins
• Toluene diisocyanate
• Talc
• Kaolin
• Diacetyl
• Oxygen
• Mercury
• Oils
• Fats
• Pyrethrum
• Nepheline
• Diatomaceous earth
• Hematite
• Copper sulfate
• Cerium
• Scandium
• Yttrium
• Lanthanum
• Cryptostroma corticale
• Aureobasidium pullulans
• Penicillium species
• Bacillus subtilis
• Bacillus cereus
• Orlon
• Polyesters
• Nylon
• Acrylic

• Occupational lung disease may be triggered by a mutation in the following genes:^[7]
  • MUC5B promoter polymorphism
    • Has been identified as causing progression in interstitial lung fibrosis
  • HLA-DPB1*0201 polymorphisms
    • Associated with chronic berylliosis, whilst HLA-DPB1*0401 gene is protective
    • Single nucleotide polymorphism in the promoter region of TNF-α, the no.308 guanine to adenine transition, has been associated with beryllium sensitization transition to clinical disease
  • NAT2 acetylation
    • Associated with bladder cancer with exposure to benzine dyes
  • HLA class II genes such as HLA-DQB1*0503
    • Associated with toluene diisocyanate-induced occupational asthma
  • Polymorphisms in exons 3 of Tyr113His (C113T) and 4 His139Arg (G139A) of the mEH gene
    • Associated with organic dust-induced chronic airways disease where the activity of microsomal epoxide hydrolase slows down

Cardiovascular	No underlying causes
Chemical/Poisoning	Orlon, polyesters, nylon, acrylic, vinyl chloride, oxygen, nitrogen oxide, sulfur dioxide, chlorine gas, methyl isocyanate, zinc, copper, manganese, cadmium, iron, magnesium, nickel, brass, selenium, tin, antimony, diphenylmethane diisocyanate, trimellitic anhydride, hydrocarbons, thermosetting resins, toluene diisocyanate, oxygen, mercury, oils, fats and pyrethrum
Dental	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	No underlying causes
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	Macropolyspora faeni, thermactinomyces vulgaris, thermactinomyces sacchari, aspergillus, cryptostroma corticale, aureobasidium pullulans, penicillium, bacillus subtilis, bacillus cereus, bird droppings, nepheline, and diatomaceous earth
Gastroenterologic	No underlying causes
Genetic	No underlying causes
Hematologic	No underlying causes
Iatrogenic	No underlying causes
Infectious Disease	Macropolyspora faeni, thermactinomyces vulgaris, thermactinomyces sacchari, aspergillus, cryptostroma corticale, aureobasidium pullulans, penicillium, bacillus subtilis, bacillus cereus, bird droppings, nepheline, and diatomaceous earth
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	No underlying causes
Nutritional/Metabolic	No underlying causes
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Ophthalmologic	No underlying causes
Overdose/Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal/Electrolyte	No underlying causes
Rheumatology/Immunology/Allergy	No underlying causes
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Miscellaneous	Coal dust, graphite, tin, aluminum, cadmium, tungsten, titanium, cobalt, iron, antimony, hematite, mixed dusts of silver and iron oxide, copper sulfate neutralized with hydrated lime, cerium, scandium, yttrium, and lanthanum

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Occupational lung disease must be differentiated from other diseases that cause shortness of breath, cough, and wheeze, such as allergic asthma, emphysema, sarcoidosis, tuberculosis, and chronic bronchitis.

Occupational lung disease must be differentiated from other diseases that cause shortness of breath, cough, and wheeze, such as allergic asthma, emphysema, sarcoidosis, tuberculosis, and chronic bronchitis.

Below is a table discussign the differential diagnoses for dyspnea with cough.

Abbreviations: ABG (arterial blood gas); ACE (angiotensin converting enzyme); BMI (body mass index); CBC (complete blood count); CSF (cerebrospinal fluid); CXR (chest X-ray); ECG (electrocardiogram); FEF (forced expiratory flow rate); FEV1 (forced expiratory volume); FVC (forced vital capacity); JVD (jugular vein distention); MCV (mean corpuscular volume); Plt (platelet); RV (residual volume); SIADH (syndrome of inappropriate antidiuretic hormone); TSH (thyroid stimulating hormone); Vt (tidal volume); WBC (white blood cell);

Organ system			Diseases	Clinical manifestations											Diagnosis					Other features
				Symptoms						Physical exam
				Loss of consciousness	Agitation	Weight loss	Fever	Chest pain	Cough	Cyanosis	Clubbing	JVD	Peripheral edema	Auscultation	CBC	ABG	Imaging	Spirometry	Gold standard
Acute Dyspnea	Respiratory system	Head and Neck, Upper airway	Angioedema[1]	–	–	–	–	–	+/-	–	+/-	–	+	Normal	Normal	↓O2, ↑CO2	Normal	N/A	Physical exam	Generalized edema
			Aspiration[2]	–	+	–	–	+/-	+	+	–	–	–	Diminished breath sounds	Normal	Normal	Atelectasis	↓Vt, ↑RV	Bronchoscopy	Choking
			Croup[3]	–	+	–	+/-	–	+	+	–	–	–	Stridor	↑WBC	Normal	Steeple sign	Normal	Physical exam	Barking cough
			Epiglottitis[4]	–	+	–	+	–	+	–	–	–	–	Stridor	↑WBC	Normal	Thumb sign	Normal	Laryngoscopy	Drooling
			Rhinosinusitis[5]	–	–	–	+	–	+/-	–	–	–	–	Normal	↑WBC	Normal	Air fluid level	Normal	Physical exam	Headache
			Vocal cord dysfunction[6]	–	–	–	–	–	+/-	–	–	–	–	Stridor	Normal	Normal	Normal	↓ FVC	Laryngoscopy	Choking sensation
		Chest and Pleura, Lower airway	Asthma attack[7]	–	+	–	–	+/-	+	+	–	–	–	Wheeze	↑ Eosinophil	Respiratory alkalosis	Normal	↓ FEV1, PEF	Physical exam and Spirometry	Chest pain
			Bronchitis[8]	–	–	–	+	+	+	–	–	–	–	Rhonchi	↑WBC	Normal	Normal	Normal	Physical exam	Rhonchi relieved by cough
			Bronchospasm[9]	+/-	+	–	–	+	+/-	+	–	–	–	Wheeze	Normal	↓O2, ↑CO2	Normal	↓Vt, ↑RV	Physical exam	Allergic reaction
			Bronchiolitis[10]	–	–	–	+	+/-	+	–	–	–	–	Wheeze and Crackles	↑WBC	Normal	Bronchovascular markings	↓Vt	Clinical assessment	Respiratory syncytial virus (RSV)
			COPD exacerbation[11]	–	+	–	+	+	+	+	+/-	+/-	+/-	Wheeze, Rhonchi, and Crackles	↑WBC, ↑RBC	Respiratory alkalosis	Hyperexpansion	↓ FEV1/FVC	Clinical assessment	Acute exacerbations of chronic bronchitis (AECB)
			Lung carcinoma[12]	–	–	+	–	–	+	+	+	–	–	Wheeze and Crackles	Normal	Normal	Mass lesion, hilar lymphadenopathy	↓Vt, ↑RV	Bronchoscopy	Paraneoplastic syndromes, such as SIADH and lambert-Eaton
			Pneumonia[13]	–	–	–	+	+	+	–	–	–	–	Wheeze, Rhonchi, and Crackles	↑WBC, neutrophilia	Normal	Lobar consolidation	Normal	Chest X-ray and CT Scan	productive cough
	Cardiovascular system		Acute heart failure[14]	+/-	+	–	–	+/-	+	+	–	+	+	S3	Normal	Respiratory alkalosis	↑ Cardiothoracic ratio	↓Vt	B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP)	Excessive sweating, high blood pressure
			Pulmonary edema[15]	+/-	+	–	+	+	+	+	+	+	+	Basal crackle	Normal	Respiratory alkalosis	Bat wing pattern, air bronchograms	↓Vt, ↑RV	Cardiac Catheterization	Tachypnea
	Toxic/Metabolic		Carbon monoxide poisoning[16]	+	–	–	–	+	+	+	–	–	–	Wheeze	Carboxyhemoglobin	↓O2, ↑CO2	Normal	N/A	Carboxyhemoglobin (HbCO) level	Headache, Dizziness, Weakness, Vomiting, Confusion
Organ system			Diseases	Clinical manifestations											Diagnosis					Other features
				Symptoms						Physical exam
				Loss of consciousness	Agitation	Weight loss	Fever	Chest pain	Cough	Cyanosis	Clubbing	JVD	Peripheral edema	Auscultation	CBC	ABG	Imaging	Spirometry	Gold standard
Chronic Dyspnea	Respiratory system	Head and Neck, Upper airway	Laryngeal adenocarcinoma[17]	–	–	+	–	–	+/-	–	–	–	–	Stridor	Normal	↓O2, ↑CO2	Retropharyngeal tissue thickness	Normal	Laryngoscopy	Choking sensation
			Vocal cord paralysis[6]	–	–	–	–	–	+/-	–	–	–	–	Stridor	Normal	Normal	Pharyngeal constrictor muscles thinning, uvular deviation	Normal	Laryngoscopy	Choking sensation
			Tracheal stenosis[18]	–	–	–	–	+/-	+/-	+	+	–	–	Stridor, Stertorous	Normal	↓O2, ↑CO2	Soft tissue thickening internal to normal-appearing tracheal cartilage	Normal	Bronchoscopy	Respiratory distress
		Chest and Pleura, Lower airway	Bronchial asthma[7]	–	+	+/-	–	+/-	+	+	+	–	–	Wheeze	↑ Eosinophil	Respiratory alkalosis, Metabolic acidosis	Pulmonary hyperinflation, Bronchial wall thickening	↓ FEV1/FVC	Spirometry before and after bronchodilator	Paroxysmal respiratory distress
			Bronchiectasis[8]	–	–	–	+	+	+	+	+	–	–	Rhonchi, Wheezing, Crackles	↑WBC, neutrophilia	↓O2, ↑CO2	Tram-track opacities	↑ FEV1/FVC	High resolution computed tomography (HRCT)	Chronic productive cough
			COPD[11]	–	–	+/-	–	–	+	+	+	+	+/-	Expiratory wheeze	↑ RBC	Respiratory alkalosis, Metabolic acidosis	↑ Bronchovascular markings, Cardiomegaly	↓ FEV1/FVC	Physical exam and Spirometry	Heavy smoking history
			Emphysema[19]	–	–	–	–	–	+/-	+	+	–	–	Expiratory wheeze, Hyperinflation	Normal	Respiratory alkalosis, Metabolic acidosis	Flattening of diaphragm, vertical heart	↓ FEV1/FVC	Physical exam and Spirometry	Barrel chest
			Pulmonary hypertension[20]	–	–	–	–	+/-	+/-	+/-	+/-	+	+	Accentuated S2	Normal	Hypoxia and acidosis	Enlarged pulmonary arteries	↑Physiologic RV	Cardiac catheterization	Syncope, Ascites, Pleural effusion
			Interstitial lung disease[21]	–	–	–	–	+	+	+	+	–	–	Rhonchi, Wheezing, Crackles	Normal	↓O2, ↑CO2	Peripheral pulmonary infiltrative opacification	↑ FEV1/FVC	High resolution computed tomography (HRCT)	Pneumoconiosis
			Sarcoidosis[22]	–	–	+/-	–	+/-	+	+	–	–	–	Crackles	Normal	↓O2, ↑CO2	Hilar adenopathy	↑ FEV1/FVC	High resolution computed tomography (HRCT)	Hypercalcemia, high ACE
			Alveolitis[23]	–	–	–	+	+	+	–	–	–	–	Basal crackle	↑WBC, neutrophilia	Normal	Basal reticulonodular opacification	↑ FEV1/FVC	High resolution computed tomography (HRCT)	Dry cough
			Bronchiolitis obliterans[10]	–	–	–	+	+	+	+	+	–	–	Expiratory wheeze	↑WBC	↓O2, ↑CO2	Hyperinflation, Reticulonodular opacities	↓ FEV1/FVC	Lung biopsy	Complication of allogeneic hematopoietic stem cell transplantation
			Cystic fibrosis[24]	–	–	+	+	–	+/-	+	+	–	–	Rhonchi, Wheezing, Crackles	Normal	Metabolic alkalosis	Thick-walled bronchiectasis	↓ FEF75%/FVC	Sweat test	Absent vas deferens
			Pulmonary right-to-left shunt[25]	–	–	–	–	+/-	+	+	+	–	–	Diminished breath sounds	Normal	↓O2, ↑CO2, Respiratory acidosis	Normal	↓Vt, ↑RV (physiological)	Pulmonary CT angiography	Chronic hypoxemia
			Diaphragmatic paralysis[26]	–	–	–	+/-	+/-	+/-	–	–	–	–	Normal	Normal	Normal	Unilateral or bilateral diaphragmatic flattening	↓Vt, ↑RV (anatomical)	CXR confirmed by fluoroscopic sniff test	Respiratory insufficiency
			Tuberculosis[27]	–	–	+	+	+	+	+/-	–	–	–	Rhonchi, Wheezing, Crackles	↑WBC	↓O2, ↑CO2	Patchy consolidation or poorly defined linear and nodular opacities	Restrictive, obstructive, or mixed	IFN-γ release assay (IGRA) Acid-fast staining	Night sweat
	Cardiovascular system		Pericardial effusion[28]	–	–	–	+/-	+	+	–	–	+	–	Muffled heart sounds	Normal	Normal	Fluid density around the heart	Normal	M-mode and 2-dimensional Doppler echocardiography	Hoarseness, Palpitation
	Systemic		Anxiety[29]	+	+	+	–	+/-	+/-	–	–	–	–	Normal	Normal	Normal	Normal	Normal	Psychological interview	Sweating, Palpitation
	Autoimmune		Churg-Strauss syndrome[30]	–	–	–	–	–	+	–	–	–	–	Scattered wheezing	Normal	Normal	Areas of parenchymal opacification	↓Vt, ↑RV	Biopsy	Fatigue,Numbness
			Wegener’s granulomatosis[31]	–	–	+/-	–	–	+	–	–	–	–	Wheezing, Crackles	↓ RBC	↓O2, ↑CO2	Cavitate nodules, ground-glass opacity	↓ FEV1/FVC	Biopsy demonstrating a granulomatous vasculitis	Chronic rhinosinusitis
			Goodpasture’s disease[32]	–	–	–	–	–	+	–	–	–	–	Bilateral coarse crepitations	↓ RBC, HGB, HCT	Normal	Like pulmonary edema	Normal	Kidney biopsy	Hematuria, Hemoptysis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Incidence, prevalence and mortality rates for occupational lung disease are not well documented and are unreliable. Individual occupational lung diseases have separate prevalence and incidence rates, such as, farmer’s lung has an incidence of 270 cases per 100,000 in 2012. Whilst the mortality rates for work-related disease are approximately 63,000 deaths in 2012. Disease manifestation is correlated to the frequency, duration and dose of inhalational exposure. Occupational lung disease has no predilection to race or gender, however, males tend to work in environments where exposure is common, therefore more males suffer from occupational lung disease. Occupational lung disease, particularly, coal worker’s pneumoconiosis is a common disease that tends to affect coal miners in West Virginia and Kentucky, USA and South Wales, UK.

There are no reliable figures for the incidence or prevalence of occupational lung disease.^{[1][2][3][4][5][6][7]}

• Farmer’s lung:
  • The incidence for farmer’s lung was 8-540 cases per 100,000 in 2012.
• Coal worker’s pneumoconiosis and silicosis:
  • Among coal workers worldwide:
    • 300 per 100, 000 developed coal worker’s pneumonconiosis
    • 25 per 100,000 developed progressive massive fibrosis
  • In 30 years of exposure, 120 per 100,000 will develop silicosis and 24 per 100,000 will die from silicosis.
• Asbestosis
  • In 1972, it was reported that 250,000 people were at risk in the US.

• There is no reliable data for the case-fatality rate of occupational lung disease.
• Mortality rates depend on the substance inhaled, as well as the frequency, duration and dose of inhalational exposure.
• Cardiopulmonary and genetic factors of the host also contribute to mortality rate.
• Overall, there was approximately 60,300 deaths from work-related disease in 2012.

Occupational lung disease commonly affects older individuals who have been exposed longer to a particular substance.

There is no racial predilection to occupational lung disease.

Males are more commonly affected by occupational lung disease than females, reflecting the occupations in which exposure is present.

• Occupational lung disease, particularly, coal worker’s pneumoconiosis is a common disease that tends to affect coal miners in West Virginia and Kentucky, USA and South Wales, UK.
• The United Kingdom, Sweden and France have a high prevalence of farmer’s lung.
• Australia, Japan, South Africa and parts of the European Union still use asbestos as an insulation material.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Common risk factors in the development of occupational lung disease include smoking, genetic susceptibility, cardiovascular disease, and frequency, intensity, and duration of exposure.

• The higher the duration, frequency, and intensity of exposure leads to an increased risk in developing occupational lung disease.^[1]
• Common risk factors in the development of occupational lung disease include:
  • Smoking
    • Weakens the immune system and leaves the body defenseless against inhaled substances
  • Cardiovascular disease
    • Also causes immunocompromisation
  • Pre-existing lung disease
    • Also causes immunocompromisation
  • Alcohol use
    • Also causes immunocompromisation
  • Genetics
    • Explains the variability in symptoms, presentation, susceptibility, and progression
  • Obesity
    • Higher risk of asthma and cardiovascular disease

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

There is insufficient evidence to recommend routine screening for occupational lung disease at a national level, however, at a local level workers with known occupational hazards benefit from a routine screening at their places of work.

There is insufficient evidence to recommend routine screening for occupational lung disease at a national level, however, at a local level workers with known occupational hazards may benefit from routine screening at their places of work. Routine screening may include:^[1][2]

• Questionnaire (including exposure assessment)
• X ray of the chest
• Spirometry
• Referral to chest clinic/specialized service for investigation and management, including:
  • Detailed history of non‐occupational factors
  • Pulmonary function testing
  • Blood tests
    • Including CBC
  • Sputum analysis
  • CT
  • Bronchoscopy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

If left untreated, patients with occupational lung disease may progress to develop pleural effusion, interstitial lung fibrosis, and lung cancer. Common complications of of occupational lung disease include interstitial pulmonary fibrosis, progressive massive fibrosis, mesothelioma, and premature death. Depending on the extent of the disease progression at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor.

• The symptoms of occupational lung disease usually develop on average in the third decade of life, and start with symptoms such as shortness of breath, fatigue, and cough.^[1]
• The symptoms of occupational lung disease typically develop 30 years after exposure to an inhalant.
• If left untreated, 30% of patients with occupational lung disease may progress to develop pleural effusion, interstitial lung fibrosis, and lung cancer.

• Common complications of occupational lung disease include:^[2][3]
  • Idiopathic pulmonary fibrosis
  • Progressive massive fibrosis
  • Mesothelioma
  • Lung cancer
  • Pulmonary hypertension
  • Respiratory failure
  • Respiratory acidosis
  • Toxemia
  • Cyanosis
  • Premature death

• Depending on the extent of the disease progression at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor.^[4]
• The presence of fibrosis is associated with a particularly poor prognosis among patients with occupational lung disease.