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Hypersensitivity Pneumonitis – Insights in ILD

 

Hypersensitivity Pneumonitis Chart – Insights in ILD

  • Occupational
  • Avocational
  • Environmental
  • Drug-induced

Hypersensitivity Pneumonitis Overview – Insights in ILD

  • Exposure-related ILDs are responsible for 20%of all ILDs1
  • These ILDs impact individuals of all ages, with the causative agent often differing between adults and children2
    • Exposure-related pediatric ILD is thought to be underestimated2
    • Misdiagnosis or underestimation of pediatric ILD often leads to diagnosis when the disease is already chronic2 
    • Most cases of pediatric ILD are due to environmental or avocational hypersensitivity pneumonitis, radiation exposure, or are drug induced2
    • Adults are often exposed within the workplace1
 
1. Glazer CS. Clin Pulm Med. 2011;18:20–28. 2. Clement A et al. Orphanet J Rare Dis. 2010;5(22):1-24.

Hypersensitivity Pneumonitis Overview (Continued) – Insights in ILD

 

Alternative Classifications of Hypersensitivity Pneumonitis – Insights in ILD

  • May account for up to 20% of all ILDs
  • Caused by exposure to agents encountered in the workplace – commonly mineral or metal dusts
  • Primary and most common pneumoconioses:
    • Asbestosis (asbestos fibers)
    • Silicosis (silica dust)
    • Coal workers’ pneumoconiosis or black lung disease (coal mine dust)1
    • Chronic beryllium disease
  • Other forms are caused by inhaling dust such as talc, mica, iron, graphite, aluminum, or barium
  
1. Glazer CS. Clin Pulm Med. 2011;18(1):20–28.

Hypersensitivity Pneumonitis Epidemiology and Survival – Insights in ILD

  • All pneumoconiosis: 260,000 deaths1
  • Understanding the epidemiology of occupational ILDs can be difficult due to2:
    • Variability in physician awareness
    • Non-standardized diagnostics
    • The potentially long delays between exposure and disease/diagnosis
Pneumoconiosis-related deaths: US 2001-20103
  • 59% Asbestosis3
  • 27% Coal Workers'3
  • 9% Other3
  • 6% Silicosis3
  • 0.2% Byssinosis3

1. GBD 2013 Mortality and Causes of Death Collaborators. Lancet. 385(9963):117–171.
2. Glazer CS et al. Clin Chest Med. 2004;25(3):467-478. 3. NIOSH 2014. Work-Related Lung Disease Surveillance System (eWoRLD). 2014-795 U.S. DHHS, CDC, NIOSH, Respiratory Health Division. https://wwwn.cdc.gov/eworld/Data/795. Accessed September 7, 2018. 

Hypersensitivity Pneumonitis Risk Factors – Insights in ILD

  • Most common symptoms in patients with significant disease1:
    • Shortness of breath
    • Cough
    • Chest tightness
    • Wheezing
  • Patients with less significant disease will have no respiratory symptoms2
  • Diagnosis is often made based on occupational history and routine CXR1
 
CXR, chest X-ray
1.Hegmann KT et al. American College of Occupational and Environmental Medicine. Occupational Interstitial Lung Disease Guideline. 2016. https://www.dir.ca.gov/dwc/MTUS/ACOEM-Guidelines/Occupational-Interstitial-Lung-Disease-Guideline.pdf. Accessed August 9, 2018. 2. Balmes JR et al. Am J Respir Crit Care Med. 2014;190(10):e34-59.
 
 

Hypersensitivity Pneumonitis Pathogenesis – Insights in ILD

  • The primary pneumoconioses typically are chronic and take many years to develop1
    • Though less common, intense exposure can cause rapidly progressing disease – particularly for silicosis1
    • The cumulative dose is the greatest factor determining ILD progression3
  • Individual physiology can impact disease progression and susceptibility3
    • Factors that impact deposition and clearance of causative agents during exposure, such as mucosal filtering, length of respiratory tract, tobacco use, and genetic characteristics, play a role3
1. Centers for Disease Control and Prevention. Pneumoconioses. https://www.cdc.gov/niosh/topics/pneumoconioses/default.html. Accessed September 7, 2018 2. Glazer CS et al. Clin Chest Med. 2004;25(3):467-478.

Hypersensitivity Pneumonitis Pathogenesis (Continued) – Insights in ILD

Lung Pathology1
Interstitial pneumonitis
Nonspecific interstitial pneumonia
Desquamative interstitial pneumonitis
Bronchiolitis obliterans/organizing pneumonia
Alveolar proteinosis
Alveolar hemorrhage
Diffuse alveolar damage
Bronchiolitis (constrictive or cellular)
Granulomatous inflammation
Lipoid pneumonia

Occupational Exposure1
Asbestos, mixed dust, uranium mining
Organic antigens
Textiles, aluminum welding, inorganic agents
Textiles
Silica or aluminum dust
Solvents, industrial chemicals
Inhalation of beryllium, cadmium, chlorine, other gas irritants
Chlorine gas, organic antigens
Beryllium, aluminum, zirconium, titanium, organic antigens
Oil-based metal working

1. Glazer CS et al. Clin Chest Med. 2004;25(3):467-478.

Subacute or Chronic HP Clinical Presentation – Insights in ILD

  • The clinical, radiologic, and pathologic presentations of occupational ILDs are similar to non-occupational ILDs due to the lung’s general response to injury1
  • A thorough, lifetime, work, and environmental history is critical to identify potential occupational exposures1
  • Characteristic radiographic changes in combination with a work history is sufficient to make diagnosis1
    • Occupational ILD should be considered for any new ILD cases in the absence of a known cause2
    • Material safety data sheets should be obtained where possible3
  • Pulmonary function tests are useful to determine severity and pharmacologic treatment  
1. Glazer CS et al. Clin Chest Med. 2004;25: 467– 478. 2. Glazer CS et al. Clin Chest Med. 2004;25(3):467-478.

Hypersensitivity Pneumonitis Diagnostic Approach – Insights in ILD

Diagnosis requires1:
  • History of exposure to a known ILD-inducing agent
  • An appropriate latency period following exposure
  • Consistent clinical disease course
  • Pattern of physiologic and radiologic evidence of disease
  • Exclusion of other known ILD-causing factors
  • Lung biopsy is not needed if these tests come back positive, butrecommended for atypical cases or cases arising from new or poorly understoodcausative agents
 1. Glazer CS et al. Clin Chest Med. 2004;25(3):467-478.
 

HP Diagnosis - Exposures History – Insights in ILD

  • After an occupational history is collected, ILD is typically detected through use of radiologic imaging, usually a CXR1
    • Spirometric testing, HRCT, sputum analysis, and bronchoalveolar lavage are also recommended1
  • The ILO provides guidelines for the systematic scientific classification of pneumoconioses2
  • The CXR is classified and scored on the following features2:
    1. Film quality
    2. Rounded small opacities (diameter)
    3. Irregular small opacities (width)
    4. Profusion (concentration of small opacities in affected area of the lung)
    5. Large opacities (longest dimension >10 mm)
 
HRCT, high- resolution computed tomography; ILO, International Labor Office.
1. Litow FK et al. J Occup Environ Med. 2015;57(11):1250-1254. 2. https://www.cdc.gov/niosh/topics/pneumoconioses/default.html
3. https://online.epocrates.com/diseases/111221/Pneumoconioses/Definition

Bacterial Antigens Associated with Hypersensitivity Pneumonitis –Insights in ILD

Exposure: Coal mine dust
Imaging:
Bronchial wall thickening
Upper lobe small nodular opacities
Lower lobe irregular opacities
Emphysema

Exposure: Silica
Imaging:
Bronchial wall thickening
Upper lobe small nodular opacities
Lower lobe irregular opacities
Emphysema

Exposure: Asbestos
Imaging:
Bronchial wall thickening
Lower lobe or diffuse irregular opacities
Rounded atelectasis

Exposure: Beryllium
Imaging:
Airway wall thickening
Perilymphatic nodules
Conglomerate opacities

1. Cox CW et al. Radiology; 2014;270(3):681-696.

Fungal Antigens Associated with Hypersensitivity Pneumonitis – Insights in ILD

Exposure History1
Dust particles
Fumes
Vapors
Gas
Farming/agriculture
Ceramics/stone/abrasives
Mining/construction

Cigarette Smoking1,2 
Male Gender2

1. American College of Occupational  and Environmental Medicine. Occupational Interstitial Lung Disease Guideline. 2016. https://www.dir.ca.gov/dwc/MTUS/ACOEM-Guidelines/Occupational-Interstitial-Lung-Disease-Guideline.pdf. Accessed August, 9, 2018. 2. Caminati A et al. Eur Respir Rev .2012;21(125):207-217.

Mycobacterial Antigens Associated with Hypersensitivity Pneumonitis –Insights in ILD

Remove exposure
  • Most occupational ILDs have no treatment with established efficacy1
  • The first line of action is to limit, or if possible, remove exposure of the causative agent1
    • Well-known agents (silica, asbestos) may have recommended exposure limits based on cumulative exposure doses1
Support
  • Symptom management includes supportive care, such as oxygen therapy, antibiotics if associated infections occur, and pulmonary rehabilitation1
Anti-inflammatories/steroids
  • Occupational ILD resulting in a specific immune response (such as CBD) may benefit from anti-inflammatory therapies such as prednisone2
Prevent
  • Management of occupational ILD in one individual also represents an important step in disease prevention – limiting or removing exposure from coworkers who also may have been exposed1

CBD, chronic beryllium disease.
1. Glazer CS et al. Clin Chest Med. 2004;25(3):467-478. 2. Glazer CS. Clin Pulm Med 2011;18(1):20–28.

Animal Protein Antigens Associated with Hypersensitivity Pneumonitis –Insights in ILD

Features of Asbestosis

Physiological findings
Interstitial fibrosis, pleural effusion, plaques in the pleural and diaphragmatic space, and pleural thickening – pleural abnormality in over 90% of patients1

Exposure
Latency of 15-40 years can result from long- or short-term exposure to asbestos fibers1

Exposure risk
Construction and building maintenance, mining, milling, ship repair or construction, automobile or railroad work, insulation work, number and duration of exposure(s)1 

Symptoms
Dyspnea, dry cough, crackles, clubbing, cor pulmonale (in advanced disease)1

Progression 
Local inflammation is activated by inflammasomes.2 Pathologic lesion begins with peribronchiolar fibrosis, extends to the alveolar wall. Cumulative or repeated exposure can influence progression1

Diagnosis
Chest radiography or CT scan, physiologic symptoms matched with slow disease course, occupational history consistent with exposure, exclusion of other ILD, biopsy not always needed1

Radiographic findings
Lower zone reticular opacity, honeycombing, pleural disease1

Treatment
No known treatment. Remove or limit exposure. Supportive care includes treatment of occurrent infections, oxygen therapy, pulmonary rehabilitation, avoidance of tobacco1

CT, computed tomography
1. Glazer CS et al. Clin Chest Med. 2004;25(3):467-478. 2. Glazer CS. Clin Pulm Med 2011;18(1):20–28.

Chemical Antigens Associated with Hypersensitivity Pneumonitis –Insights in ILD

Features of Silicosis
 
Physiological findings
3 forms can develop depending on exposure: chronic simple (most common), accelerated, and acute1

Exposure
Inhalation of crystalline silica or silica dust. Chronic simple: latency of 10-40 y; accelerated: higher exposure, latency of 5-10 y; acute: high exposure over months to 2 years1

Exposure risk
Mining, construction, tunneling or road work, sandblasting, foundry or granite/stone work, production of silica flour, ceramics, or glass1 

Symptoms
Dyspnea, productive cough, pulmonary obstruction/restriction1

Progression 
Local inflammation is activated by inflammasomes.2 Chronic simple, accelerated, and acute silicosis have a similar presentation with increasing severity. The adjoining of individual nodules results in complicated silicosis. Masses of fibrosis can develop in both chronic simple and accelerated silicosis. Acute silicosis presents similarly to alveolar proteinosis. Exposure increases risk of developing other lung diseases, infection such as tuberculosis, cancers, and certain autoimmune disorders1

Diagnosis
Chest X-ray or CT scan, biopsy not always needed1

Radiographic findings
Upper lobe nodular opacities, hilar adenopathy (10% cases show an eggshell pattern), <5mm pulmonary nodules (individual or coalesced, ie, fibrosis masses >1cm), fibrotic lesions1

Treatment
No successful treatment available, supportive care and removal from exposure similar to asbestosis. Screening for tuberculosis infection recommended1

1. Glazer CS et al. Clin Chest Med. 2004;25(3):467-478. 2. Glazer CS. Clin Pulm Med 2011;18(1):20–28.

Hypersensitivity Pneumonitis HRCT – Insights in ILD

Despite declining usage of coal, increased mechanization, and an associated decrease in rates of coal-related lung disease since the 1970s, mining continues to present a substantial health risk1

Features of Coal-Exposure Related ILD
 
Physiological findings
Pneumoconiosis, chronic airway diseases with restrictive, obstructive, or mixed-pattern pulmonary function, emphysema, abnormal gas exchange, chronic bronchitis (estimated to occur in 35% of US coal miners)

Exposure
Inhalation of coal mine dust

Exposure risk
Coal mining – continues to represent a large source of employment in the United States, China, and worldwide

Symptoms
Cough, productive sputum, shortness of breath, wheezing, emphysema

Progression 
Coal dust induces inflammatory responses and fibrosis via the release of cytokines. Disease can progress from pneumoconiosis to massive fibrosis, emphysema, and chronic bronchitis. Disease progression can be exacerbated by tobacco use and exposure to silica dust

Diagnosis
Occupational history, radiographic chest X-rays or CT scans, pulmonary function tests. Lung biopsy positive for inflammatory and fibrotic lesions with associated emphysema can confirm diagnosis

Radiographic findings
Nodules in the upper zone, progressive fibrosis, fibrotic scars, irregular opacities

Treatment
No specific treatment. Focus is on removal or reduction of exposure, prevention with proper protective gear, and surveillance programs to monitor health. Supportive care and occasionally whole-lung lavage have been used

1. Petsonk EL et al. Am J Respir Crit Care Med. 187(11): 1178–1185.

Hypersensitivity Pneumonitis Histopathology – Insights in ILD

Features of CBD
 
Physiological findings
Granulomatous disease similar to sarcoidosis occurring after exposure and sensitization to beryllium. Primarily impacts the lung, but can affect other organs as well

Exposure
Dust or fumes of pure beryllium, beryllium alloy, or beryllium oxides. Sensitization in 2%-10% of people exposed. Wide ranging latency of 2 months to 40 years

Exposure risk
Sensitization to antigens can increase susceptibility to developing ILD with continued exposure. Exposure often occurs when working with nuclear weapons, aerospace, and defense industries, electronics, ceramics, metal recycling and alloy working, dental prostheses manufacture, living or working near beryllium production facility

Symptoms
Can be asymptomatic, or cause dyspnea, dry cough, fatigue, weight loss, fever, night sweats, myalgias, crackles, subcutaneous nodules; in advanced cases, also cyanosis, clubbing of the digits, heart failure, pulmonary obstruction/restriction, ventilation and gas exchange abnormalities during cardiovascular exercise

Progression 
Exposure activates the adoptive and innate immune response. Most patients progress slowly while otherspresent rapidly

Diagnosis
Beryllium lymphocyte proliferation test, history of exposure, reaction to beryllium on blood or bronchoalveolar lavage, lung inflammation on bronchoscopy or chest X-ray/CT scan

Radiographic findings
Similar to sarcoidosis, diffuse bilateral opacities, nodules in the middle and upper pulmonary zone, hilar adenopathy (20%-30% of cases), honeycombing and/or masses and emphysema can occur in advanced cases

Treatment
Removal from exposure and corticosteroid treatment, along with supportive care

1. Glazer CS et al. Occupational interstitial lung disease. Clin Chest Med. 25 (2004) 467– 478.

Hypersensitivity Pneumonitis Treatment Recommendations – Insights in ILD

  • Common source of avocational ILD arises among bird owners, termed bird fancier’s disease1
    • Bird fancier’s disease can be caused by exposure to antigens found in bird droppings or feathers1
  • Exposure to man-made mineral fibers (eg, manufactured, artificial fibers; glass fiber-reinforced plastic) may be a growing concern, as these fibers can have similar characteristics to asbestos2
1. Clement A et al. Interstitial lung diseases in children. Orphanet J Rare Dis. 2010. 5(22). 2. Fireman E. Man-made mineral fibers and interstitial lung diseases. Current Opinion in Pulmonary Medicine. 2014, 20(2). 

Hypersensitivity Pneumonitis Summary – Insights in ILD