Chapter 13: Pneumoconioses, sarcoidosis and pneumonitis

Question 1

What is pneumociniosis?

Answer 1

Pneumoconiosis is a term originally coined to describe lung disorders caused by inhalation of mineral dusts. The term has been broadened to include diseases induced by organic and inorganic particulates, and some experts also regard chemical fume- and vapor-induced lung diseases as pneumoconioses

Question 2

Name three mineral dust-induced lung diseases.

Answer 2

Pneumoconiosis (coal dust), silicosis (silica), asbestosis (asbestos)

Question 3

What influences the reaction of the lung against dust particles?

Answer 3

It depends on many variables, including the size, shape, solubility, and reactivity of the particles.
For example, particles greater than 5 to 10 μm are unlikely to reach distal airways, whereas particles smaller than 0.5 μm move into and out of alveoli, often without substantial deposition and injury. Particles that are 1 to 5 μm in diameter are the most dangerous, because they get lodged at the bifurcation of the distal airways.

Coal dust is inert, but silica and asbestos are more reactive.

Question 4

What cell plays a key cellular element in the initiation and perpetuation of inflammation, lung injury and fibrosis?

Answer 4

Pulmonary alveolar macrophage

Question 5

What other cells, besides the macrophage, are activated in inflammation, lung injury and fibrosis and where does this lead to?

Answer 5

Following phagocytosis by macrophages, many particles activate the inflammasome and induce production of the pro-inflammatory cytokine IL-1 as well as the release of other factors, which initiates an inflammatory response that leads to fibroblast proliferation and collagen deposition

Question 6

If you want to read more about coal worker’s pneumoconiosis, silicosis and asbestosis

Answer 6

go to p509-511

Question 7

What is sarcoidosis?

Answer 7

Sarcoidosis is a multisystem disease of unknown etiology characterized by noncaseating granulomatous inflammation in many tissues and organs

Question 8

Is sarcoidosis a restrictive or obstructive lung disease?

Answer 8

One presentation of sarcoidosis is a restrictive. Other diseases, including mycobacterial or fungal infections and berylliosis, sometimes also produce noncaseating granulomas; therefore, the histologic diagnosis of sarcoidosis is one of exclusion

Question 9

Sarcoidosis can manifest in many different ways, but what is the major finding at presentation in most cases?

Answer 9

Bilateral hilar lymphadenopathy or lung involvement (or both), visible on chest radiographs

Question 10

The etiology of sarcoidosis remains unkown, but there are some suggestions.. which?

Answer 10

Disordered immune regulation in genetically predisposed individuals exposed to certain environmental agents

Question 11

Several immunologic abnormalities in sarcoidosis suggest the development of a cell-mediated response to an unidentified antigen. The process is driven by CD4+ helper T cells. These immunologic “clues” include the following:

(just read the following card, don’t learn)

Answer 11

• Intraalveolar and interstitial accumulation of CD4+ TH1
cells, with peripheral T cell cytopenia
• Oligoclonal expansion of CD4+ TH1 T cells within the
lung as determined by analysis of T cell receptor
rearrangements
• Increases in TH1 cytokines such as IL-2 and IFN-γ, resulting in T cell proliferation and macrophage activation,
respectively
• Increases in several cytokines in the local environment
(IL-8, TNF, macrophage inflammatory protein-1α) that favor recruitment of additional T cells and monocytes and contribute to the formation of granulomas
• Anergy to common skin test antigens such as Candida or purified protein derivative (PPD)
• Polyclonal hypergammaglobulinemia
• Familial and racial clustering of cases, suggesting the
involvement of genetic factors

Question 12

After a lung transplantation for sarcoidosis, can sarcoidosis recur?

Answer 12

Yes, in 1/3 of the patients, but without any effect on survival

Question 13

For the morphology of sarcoidosis, see p513

Answer 13

It is not included since I don’t seem it relevant / was not discussed in the lecture

Question 14

What are the clinical features of sarcoidosis?

Answer 14

• In many affected individuals, the disease is entirely asymptomatic, discovered on routine chest films as bilateral hilar adenopathy or as an incidental finding at autopsy.
• In others, peripheral lymphadenopathy, cutaneous lesions, eye involvement, splenomegaly, or hepatomegaly may be presenting manifestations. In about two-thirds of symptomatic cases, there is gradual appearance of respiratory symptoms (shortness of breath, dry cough, or vague substernal discomfort) or constitutional signs and symptoms (fever, fatigue, weight loss, anorexia, night sweats)

Question 15

How is sarcoidosis diagnosed?

Answer 15

A definitive diagnostic test for sarcoidosis does not exist, and establishing a diagnosis requires the presence of clinical and radiologic findings that are consistent with the disease, the exclusion of other disorders with similar presentations, and the identification of noncaseating granulomas in involved tissues. In particular, tuberculosis must be excluded (!)

Question 16

What is hypersensitivity pneumonitis?

Answer 16

Hypersensitivity pneumonitis is an immunologically mediated inflammatory lung disease that primarily affects the alveoli and is therefore often called allergic alveolitis. Most often it is an occupational disease that results from heightened sensitivity to inhaled antigens such as those found in moldy hay

Question 17

What is the difference between hypersensitive pneumonitis and bronchial asthma?

Answer 17

Bronchial asthma: bronchi are the focus of immunologically mediated injury,
Hypersentivity pneumonitis: the damage occurs at the level of alveoli

Question 18

How does hypersensitive pneumonitis manifest (restrictive/obstructive, clinical characteristics)?

Answer 18

It manifests predominantly as a restrictive lung disease (because it mostly affects the alveoli) with the typical decreases in diffusion capacity, lung compliance, and total lung volume. (The responsible occupational and house- hold exposures are diverse, but the syndromes share common clinical and pathologic findings and probably have a very similar pathophysiologic basis)

Question 19

What are some sources of antigens that cause hypersensitivity pneumonitis?

Answer 19

• mushrooms, fungi, yeasts
• bacteria
• mycobacteria
• birds
• chemicals

Question 20

What are several lines of evidence that suggest hypersensitivity pneumonitis is an immunologically mediated disease?

(for illustration, just read/don’t learn)

Answer 20

• Bronchoalveolar lavage specimens consistently show increased numbers of CD4+ and CD8+ T lymphocytes.
• Most affected patients have specific antibodies against the offending antigen in their serum.
• Complement and immunoglobulins have been demonstrated within vessel walls by immunofluorescence.
• Noncaseating granulomas are found in the lungs of two-thirds of affected patients.

Question 21

What are the clinical features of hypersensitivity pneumonitis?

Answer 21

Hypersensitivity pneumonitis may manifest either as an acute reaction, with fever, cough, dyspnea, and constitutional signs and symptoms arising 4 to 8 hours after exposure, or as a chronic disease characterized by insidious onset of cough, dyspnea, malaise, and weight loss.

Question 22

What is pulmonary eosinophilia?

Answer 22

A number of disorders characterized by pulmonary infiltrates rich in eosinophils, which are recruited to the lung by local release of chemotactic factors

Question 23

In what categories is pulmonary eosinophilia divided into?

i don’t think you should know this

Answer 23

• Acute eosinophilic pneumonia with respiratory failure
• Simple pulmonary eosinophilia (Loeffler syndrome)
• Tropical eosinophilia
• Secondary eosinophilia
• Idiopathic chronic eosinophilic pneumonia

for the explanations see p515

Question 24

In addition to obstructive lung disease (COPD), smoking is also is associated with restrictive or interstitial lung diseases. Such as which?

Answer 24

Desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis

Question 25

What are histologic features of smoking-related interstitial diseases?

Answer 25

The accumulation of large numbers of macrophages containing dusty-brown pigment (smoker’s macrophages) in the air spaces. The alveolar septa are thickened by a sparse inflammatory infiltrate (usually lymphocytes); interstitial fibrosis, when present, is mild