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I&I WC1 > Pulmonology > Flashcards

Pulmonology Flashcards

1
Q

Which anatomical structures are considered part of the upper respiratory tract (URT)? (3)

A
  1. Nose
  2. Sinuses
  3. Pharynx
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2
Q

Into which three parts is the pharynx subdivided?

A
  1. Nasopharynx
  2. Oropharynx
  3. Hypopharynx
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3
Q

Which anatomical structures are considered part of the lower respiratory tract? (LRT) (4)

A
  1. Larynx
  2. Trachea
  3. Bronchus/bronchioli
  4. Lung
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4
Q

What kind of epithelium can be found in the trachea?

A

Respiratory epithelium -> cilindrical ciliated epithelium

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5
Q

What is the shape of cartilage bands in the trachea?

A

C-shaped

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6
Q

What is the opening in the C-shaped cartilage bands in the trachea filled with?

A

Smooth muscle tissue connecting both sides of the C-shape

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7
Q

How many generations of branching can be found in the bronchial system?

A

~24

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8
Q

Into which two regions can the bronchial system be divided?

A
  1. Non-respiratory
  2. Respiratory
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9
Q

Which bronchi & bronchioli are part of the non-respiratory bronchial system? (3)

A
  1. Bronchus
  2. Segmental bronchioli
  3. Non-respiratory subsegmental bronchioli
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10
Q

What is the size cut-off between a bronchus and a bronchiolius?

A

Bronchus >1 cm, bronchiolus <1 cm

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11
Q

Which structures are part of the respiratory bronchial system? (3)

A
  1. Respiratory subsegmental bronchioli
  2. Alveolar ducts
  3. Alveolar sacs
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12
Q

Into how many segments is the left/right lung divided?

A

Left = 9
Right = 10

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13
Q

Which cell types can be found in the bronchus? (5)

A
  1. Cylindric ciliated epithelium
  2. Goblet cells
  3. Basal cells
  4. Neuro-endocrine cells
  5. Club cells
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14
Q

What is the function of the cilia of respiratory epithelium?

A

Beat to remove particulate matters from the respiratory tract

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15
Q

What is the beating frequency of the cilia of respiratory epithelium? What does this frequency depend on?

A

~20x/second, depending on outside temperature (lower = slower)

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16
Q

What is the function of goblet cells?

A

Production of mucin

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17
Q

Where is most mucus in the respiratory tract produced?

A

Bronchial glands

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18
Q

What is the function of basal cells in the respiratory tract?

A

Stem cells for respiratory epithelium

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19
Q

How are basal cells connected to the basal lamina?

A

Hemi-desmosomes

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20
Q

What is the function of neuro-endocrine cells in the respiratory tract?

A

Important in the development of the lungs

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21
Q

Neuro-endocrine cells are present in [low numbers/high numbers] in healthy situations. During inflammation, their number [decreases/increases]

A

Healthy: low numbers
Inflammation: increase of neuro-endocrine cells

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22
Q

How can neuro-endocrine cells be visualized during histology?

A

Immunohistochemical staining

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23
Q

In which bronchi can club cells be found?

A

Smaller bronchioles

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24
Q

What are the functions of club cells? (4)

A
  1. Modulation of inflammatory reactions
  2. Metabolism of inhaled toxic substances
  3. Surfactant production
  4. Stem cells for ciliated/mucous cells
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25
Q

Squamous epithelial cells [are/are not] present in healthy respiratory tracts

A

Not present; presence of squamous epithelium = metaplasia

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26
Q

Where in the respiratory tract can bronchial glands be found?

A

Medium-sized bronchioles, large bronchioles & bronchi

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27
Q

Why is it harder to move mucus higher up in the respiratory tract, compared to the smaller structures deep in the respiratory tract?

A

Lower surface area = less cilia to move mucus

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28
Q

Which system influences the density of mucus in the respiratory tract?

A

CFTR ion transporter

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29
Q

Mucus consists of two-layers with different viscosity. What is the lower layer called, and is it more or less viscous than the upper layer.

A

Hypophase -> less viscous than upper layer, allowing cilia to move

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30
Q

What is the functional unit into which the lungs are divided? How is this determined?

A

Pulmonary acini/primary pulmonary lobule -> this is the area originating from 1 respiratory bronchiole

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31
Q

How many alveoli does a pulmonary acinus contain on average?

A

~2000

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32
Q

What is the smallest identifiable component of the lung? How is this determined?

A

Lobule/secondary pulmonary lobule -> the area originating from 1 terminal bronchiole (=bigger than acinus!)

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33
Q

How many acini does a lobule contain?

A

3-30

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34
Q

How are alveoli connected in the lung? What is their physiological function? Why are they important for pathology?

A

Pores of Kohn form connections between the alveoli
Physiological function: allow air to pass between alveoli in case of obstructions
In a pathological setting, pathogens (bacteria) can use these pores to spread throughout a whole lobe of the lung

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35
Q

Which two cell types can be found in the alveoli of the lung?

A
  1. Type I pneumocyte
  2. Type II pneumocyte
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36
Q

What is the function of type I pneumocytes?

A

Gas exchange (thin cells that allow for diffusion)

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37
Q

What are the functions of type II pneumocytes? (2)

A
  1. Surfactant production
  2. Replacement of damaged type I pneumocytes
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38
Q

Which type of pneumocyte covers the majority of the surface of the alveoli? How many % of the surface?

A

Type I pneumocyte, 95%

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39
Q

Which is more abundant: type I pneumocyte/type II pneumocyte

A

Type II pneumocyte (even though type I pneumocytes cover the majority of the surface)

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40
Q

In addition to cells, which structure can be found in the alveoli?

A

Interstitium

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41
Q

Which immune cells can be found throughout the alveoli of the lung?

A

Alveolar macrophages

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42
Q

Which staining is used to visualize connective tissues in the lung?

A

Elastica van Gieson (EvG)

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43
Q

What are age-related normal changes of the lungs? (9)

A
  1. Ossification of tracheal/bronchial cartilage
  2. Epithelial metaplasia in bronchial glands
  3. Pulmonary arterial/venous intimal thickening
  4. Alveolar enlargement = senile emphysema
  5. Medial calcification in bronchial arteries
  6. Senile vascular amyloidosis
  7. Anthracosis
  8. Pleural plaques
  9. Apical cap
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44
Q

What makes the lung easy to enter for pathogens? (2)

A
  1. Large interface with the environment
  2. Highly vascularized, allowing blood-borne pathogens to enter
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45
Q

Which stainings are used to identify bacterial infections of the lung? (3)

A
  1. Gram
  2. PAS
  3. Ziehl-Neelsen/auramine
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46
Q

What do Ziehl-Neelsen/auramine stainings reveal?

A

Mycobacteria

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47
Q

Which stainings are used to identify fungal infections of the lung? (3)

A
  1. PAS/PAS-D
  2. Grocott
  3. Immunohistochemistry
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48
Q

Which staining can be used to identify viral infections of the lung?

A

Immunohistochemistry

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49
Q

What are conditions that predispose for infections of the lung? (4)

A
  1. Impairment of pulmonary defence mechanisms
  2. Lowered host resistance
  3. Unusually virulent pathogens
  4. Being hospitalized
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50
Q

Which defence mechanisms are present in the respiratory tract? (4)

A
  1. Clearing mechanisms -> coughing, sneezing
  2. Mucociliary apparatus
  3. Phagocytic/bactericidal action
  4. Oedema/congestion
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51
Q

What kind of respiratory infections are often abundant in case of defects of innate/humoral immunity?

A

Pyogenic infections

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52
Q

What kind of respiratory infections are often abundant in case of defects of cellular immunity?

A

Intracellular organisms & low-virulent organisms

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53
Q

Viral pneumonia is often [self-limiting/severe/deadly]

A

Often self-limiting

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54
Q

What often happens when a viral pneumonia becomes very severe?

A

Bacterial superinfection

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55
Q

Into which major groups can viral infections of the respiratory tract be divided? (3)

A
  1. Specific/restricted to respiratory tract
  2. Systemic infections involving the lung
  3. Opportunistic infections
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56
Q

What are viruses targeting the URT? (5)

A
  1. Rhinovirus
  2. Coronavirus
  3. Influenza virus
  4. RSV
  5. Adenovirus
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57
Q

What are viruses targeting the LRT? (4)

A
  1. Influenza virus
  2. RSV
  3. Adenovirus
  4. Metapneumovirus
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58
Q

Systemic infections by which viral families can also cause respiratory symptoms? (3)

A
  1. Herpesviruses
  2. Paramyxoviruses
  3. Togaviridae
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59
Q

True or false: viral respiratory inections can by easily distinguished through histology

A

False; limited morphological specificity in viral pulmonary infections

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60
Q

Which histological pattern is often seen in viral infection of the lung?

A

Interstitial lymphocytic pattern with diffuse alveolar damage

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61
Q

What is sarcoidosis (definition)?

A

Granulomatous disorder of unkown cause, affecting multiple organs

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62
Q

Why is sarcoidosis difficult to diagnose?

A

It can resemble many other diseases

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63
Q

Which locations of sarcoidosis often have most severe complications? (2) Does sarcoidosis often occur in these areas?

A
  1. Heart
  2. CNS

Sarcoidosis in these locations is rare

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64
Q

Which organs are most often affected by sarcoidosis? (3) What is a common factor between these organs?

A
  1. Lung
  2. Skin
  3. Eyes

All three exposed to outside air

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65
Q

What is the M:F ratio of sarcoidosis?

A

1:1

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66
Q

Men are often affected by sarcoidosis at an [older/younger] age, whereas women are affected [older/younger]

A

Men = younger
Women = older

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67
Q

How many % of sarcoidosis cases resolves itself, and how many % become chronic?

A

50/50

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68
Q

What is an acutely presenting form of sarcoidosis? Where does it often occur?

A

Löfgrens syndrome, often occurs in Scandinavia

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69
Q

What is the prognosis of Löfgrens syndrome?

A

Good prognosis

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70
Q

What is the treatment strategy of low-risk sarcoidosis?

A

Observe, treat when necessary

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71
Q

How many patients within a low-risk group of sarcoidosis go into remission within 2 years?

A

60-70%

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72
Q

What is the treatment strategy of intermediate-risk sarcoidosis?

A

Treat with low dose glucocorticoids, but try to maintain best quality of life

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73
Q

How can treatment of intermediate-risk sarcoidosis be escalated, if needed?

A

DMARDs or anti-TNF

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74
Q

What is the treatment strategy of high-risk sarcoidosis?

A

Aggressive treatment using high dose corticosteroids with methotrexate

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75
Q

What is the hallmark of sarcoidosis?

A

Granuloma formation

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76
Q

What is the structural makeup of a granuloma?

A

Core of histiocytes (=macrophages), surrounded by fibroblasts & T-cells

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77
Q

When do granulomas normally form?

A

When a foreign object cannot be cleared by the immune system and needs to be encapsulated

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78
Q

What is the disadvantage of using anti-inflammatory treatments in case of granulomatous disease?

A

It could reactivate disease (such as tuberculosis) that is encapsulated in these granulomas

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79
Q

What is the antigen causing granuloma formation in sarcoidosis?

A

Antigen unknown

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80
Q

How many % of affected individuals die due to progressive sarcoidosis?

A

1-5%

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81
Q

What are causes of death due to sarcoidosis? (3)

A
  1. CNS involvement
  2. Cardial involvement
  3. Respiratory failure
82
Q

Which cell type is found in high numbers in BALF of sarcoidosis patients?

A

Th17.1 cells -> Th17-cells secreting IFN-γ

83
Q

Which cytokine is strongly involved in granuloma formation?

A

IFN-γ

84
Q

Are the Th17.1 cells found in the BALF of sarcoidosis patients also found in peripheral blood?

A

No -> increased amount of Th17 cells, but not Th17.1

85
Q

High amounts of Th17-cells in BALF is [favourable/unfavourable] from a prognostic point of view (sarcoidosis)

A

Unfavourable -> worse prognosis

86
Q

What is an immunological characteristic that can be found in patients with active chronic sarcoidosis >2 years?

A

Increased numbers of active and naïve T-cells

87
Q

Which activation marker is expressed in high amounts in patients with active chronic sarcoidosis?

A

CD25

88
Q

CTLA-4 is expressed in [lower/higher] numbers in sarcoidosis patients with worse prognosis. What is the effect of this?

A

Lower -> less inhibition = more activation, especially on Th17-cells

89
Q

Why can anti-CTLA-4 ICIs provoke sarcoidosis?

A

They block co-inhibition, sometimes allowing for activation of cells that cause sarcoidosis

90
Q

Which groups of drugs can be used to target sarcoidosis? (2)

A
  1. CTLA4 stimulation
  2. Targeting of involved cytokines
91
Q

What are current challenges in sarcoidosis research? (3)

A
  1. Identifying patient subsets according to trigger, organ involvement and disease course
  2. Finding ways to sample blood for diagnosis and follow-up
  3. Developing a good mouse model with immunological characteristics
92
Q

What are symptoms of asthma? (3)

A
  1. Shortness of breath
  2. Chest tightness/pain
  3. Wheezing when exhaling
93
Q

What causes asthma symptoms?

A

Chronic inflammation of the airways

94
Q

How many people are affected by asthma worldwide? How many deaths/year?

A

~340 million affected, leading to ~500.000 deaths/year

95
Q

What is the first line clinical management of asthma?

A

Corticosteroids + bronchodilators

96
Q

What is the mechanism of action of corticosteroids in asthma?

A

Suppression of pulmonary immune system

97
Q

True or false: all asthma patients respond to corticosteroids

A

False; this is dependent on disease phenotype

98
Q

What is the downside of the use of corticosteroids in asthma?

A

Severe side-effects

99
Q

Which class of drugs is used as bronchodilators in asthma? What is their mechanism of action?

A

β2-agonists, relaxing the smooth muscle cells of the airway wall

100
Q

Why are first line drugs for asthma inhaled?

A

Local release

101
Q

How many % of asthma patients show no symptom control on first line treatment?

A

5-15%

102
Q

What is a frequent trigger for asthma exacerbations?

A

Respiratory infections

103
Q

What are the hallmarks of asthma? (2)

A
  1. Airway hyperresponsiveness
  2. Bronchoconstriction
104
Q

What is the result of airway remodelling in asthma?

A

Narrower airways

105
Q

Which remodelling processes take place in airway remodelling in asthma? (5)

A
  1. Hyperplasia of epithelial cells
  2. Subepithelial fibrosis through collagen deposition
  3. Increased numbers of goblet cells
  4. Hyerplasia & hyperthrophy of submucosal glands
  5. Increased volume of submucosal glands
106
Q

True or false: remodelling of the airway in asthma can be reverted with treatment

A

True and false -> remodelling is partly reversible, but severe remodelling will not be fully restored on treatment

107
Q

What are the processes that constitute an asthma attack?

A
  1. Tightening of smooth muscles
  2. Production of mucus
108
Q

What is the underlying mechanisms that triggers an asthma attack?

A

Mast cell degranulation

109
Q

Mast cell degranulation plays an important role in asthma. Why are anti-histamine therapies not used in asthma? (2)

A
  1. Side effects
  2. Only has effect late in asthma pathophysiology -> only works if mast cells are alreay present in the lungs
110
Q

Into which two (immunological) subtypes can asthma roughly be divided? How many % of patients fall into each group?

A
  1. T2-low asthma = 40%
  2. T2-high asthma = 60%
111
Q

What are triggers of T2-low asthma?

A

Non-allergic type -> triggered by smoking or infections

112
Q

What are the main cell types (4) and cytokines (2) involved in T2-low asthma?

A

Cell types: Th1, Th17, ILC1, ILC3
Cytokines: IFN-γ, IL-17

113
Q

What kind of granulocytes are involved in T2-low asthma?

A

Neutrophilic inflammation

114
Q

What are triggers of T2-high asthma?

A

Allergic triggers

115
Q

What are the main cell types (2) and cytokines (4) involved in T2-high asthma?

A

Cell types: Th2, ILC2
Cytokines: IL-4, IL-5, IL-13, IL-9

116
Q

What kind of granulocytes are involved in T2-high asthma?

A

Eosinophils

117
Q

What is the effect of IL-4 on B-cells? What does this result in?

A

Class switch to IgE -> can lead to antigen-specific mast cell degranulation through FcεR

118
Q

Which two arms of activation of asthma-related cells are there in T2-high asthma?

A
  1. Epithelial response leads to damage and activation of epithelial cells
  2. Activation of Th2-cells through antigen presentation of allergens by DCs
119
Q

What is the process in which the epithelium drives T2-high asthma? (3 steps)

A
  1. Damage to epithelium due to proteases in allergens + triggering of TLRs on epithelial cells by allergens
  2. Production of alarmins by epithelial cells
  3. Alarmins activate ILC2s in epithelium -> release of type II cytokines
120
Q

Which alarmins are produced by the epithelium in T2-high asthma when the epithelium is triggered by allergens? (3)

A

IL-25, IL-33, TSLP

121
Q

What are the effects of IL-4 in T2-high asthma? (3) Some of these are a collaboration between with another cytokine. Which?

A
  1. Class switching to IgE
  2. Activation of M2-macrophages (together with IL-13)
  3. Recruitment of mast cells (together with IL-9)
122
Q

What are the effects of IL-5 in T2-high asthma? (2)

A
  1. Eosinophil recruitment
  2. Increased eosinophil production in bone marrow
123
Q

What is the effect of IL-9 in T2-high asthma? With cytokine contributes to this process?

A

Recruitment of mast cells, together with IL-4

124
Q

What is the effect of IL-13 in T2-high asthma? (4) Some of these are a collaboration between with another cytokine. Which?

A
  1. Disruption of epithelial homeostasis, causing it to be easily triggered by allergens
  2. Activation & migration of DCs to lymph nodes, where they activate T2-cells
  3. Activation of M2-macrophages (together with IL-4)
  4. Induces differentiation of goblet cells, causing goblet hyperplasia
125
Q

Asthma symptoms are ofte more severe [higher up in the gas conduction system/deeper in the lung]. Why?

A

Higher up in the gas conduction system -> higher amount of harmful substances

126
Q

What defines an innate lymphoid cell?

A

No expression of lineage markers

127
Q

Which ILC is important in T2-high asthma?

A

ILC2

128
Q

How are ILC2s activated in T2-high asthma?

A

Activated by alarmins produced by epithelium (IL-33, IL-25, TSLP)

129
Q

Which epithelial cells produce high amounts of alarmins upon triggering by allergens in T2-high asthma?

A

Tuft cells -> produce high amounts of IL-25

130
Q

How can ILC2s be stained?

A

Lineage negative cells that express IL7R and CRTh2

131
Q

How do ILC2s collaborate with Th2-cells in case or strong allergens?

A

Release of type II cytokines when triggered by alarmins produced by epithelum -> IL-13 released by ILC2s activates DCs that activate T-cells in lymph nodes

132
Q

What are examples of strong allergens? (2)

A

Moulds, proteases

133
Q

How do ILC2s collaborate with Th2-cells in case of mild allergens?

A

DCs pick up allergens and activate to lymph nodes to activate Th2-cells. Th2-cells migrate to lung and start inflammatory response, after which ILC2s join in.

134
Q

What is an example of a mild allergen?

A

House dust mite

135
Q

What are the characteristics of ILC2s involved in activation of Th2-cells in case of a strong allergen?

A
  1. Essential sources of IL-5, IL-13
  2. Activated in absence of T-cells
  3. Essential for DC migration to draining LN
  4. High in CD25, ICOS, IL-33R & KLRG1
136
Q

What are the characteristics of ILC2s involved in reactions against milder allergens? (4)

A
  1. Not early sources of IL-5, IL-13
  2. Dependent on T-cells for induction
  3. Present in chronic airway inflammation
  4. Low in CD25, ICOS, IL-33R & KLRG1
137
Q

Why is it difficult to study the role of ILC2s in T2-high asthma?

A

Only present in very low numbers in blood and tissue + tissue is hard to obtain

138
Q

What are activation markers of ILCs? Which cell type has the same activation markers?

A

CD45RA = inactive
CD45RO = active -> produce cytokines upon activation

This is also true for memory T-cells

139
Q

Which cells can be found in increased amounts in blood of T2-high asthma patients? Does this also correlate with disease severity?

A

CD45RO+ ILC2s (=activated ILC2s)
This correlates with disease severity -> higher numbers = worse

140
Q

Patients with T2-high asthma with high amounts of activated ILC2s in their blood respond [better/worse] to medication than persons with lower numbers of activated ILC2s

A

Worse response in case of high activated ILC2s

141
Q

What is the role of CD8+ T-cells in T2-high asthma? (hypothesis)

A

Under asthmatic circumstances, CD8+ cells produce type II cytokines instead of IFN-γ -> exacerbates disease

142
Q

What is paradoxical about the fact that CD8+ T-cells can cause asthma excerbations?

A

CD8+ T-cells normally produce IFN-γ, which should suppress the T2-response leading to asthma

143
Q

Why do CD8+ T-cells that produce type II cytokines respond poorly to treatment?

A

They are not very sensitive to steroids

144
Q

What are symptoms of interstitial lung diseases? (4)

A
  1. Shortness of breath
  2. Fatigue
  3. Coughing (in some patients)
  4. Respiratory failure
145
Q

What is the only curative treatment for interstitial lung diseases?

A

Lung transplantation

146
Q

What are major groups of interstitial lung diseases? (4) How many % of ILD patients belong to each group?

A
  1. Sarcoidosis = ~50%
  2. Interstitial idiopathic pneumonias = ~20%
  3. Auto-immune diseases = ~20%
  4. Exposure-related ILD
147
Q

What are the common phases of ILDs? (3)

A
  1. Genetic predisposition & aging as risk factors, environmental factors as a trigger
  2. Early phase = inflammation
  3. Late phase = fibrosis
148
Q

Where is inflammation located when ILD is triggered by environmental factors in the airways?

A

Epithelial cells, which become fibrotic

148
Q

Where is inflammation located when ILD is triggered by auto-immune disease?

A

Endothelium of lung capillaries

149
Q

True or false: fibrotic processes in all kinds of ILD are similar, even if their aetiology differs

A

True; once the fibrotic phase of ILD starts, this is nearly the same for all ILDs

150
Q

What causes fibrotic processes in ILD? How is it exacerbated?

A

Recurrent tissue damage causes fibrosis
Fibrosis causes lung tissue to stiffen, leading to additional damage -> in turn increases fibrosis

151
Q

Where in the lung does fibrosis often start in ILD

A

Subpleural, then spreading throughout the lung

152
Q

True or false: the inflammation phase of ILDs can be dampened/stopped, thus preventing fibrosis from occurring

A

True; at the inflammatory stage, fibrosis can still be prevented by stopping inflammatory underlying mechanisms

153
Q

True or false: the fibrosis phase of ILDs can be stopped, allowing for the damage to be undone

A

False; one fibrosis has started, this process can only be slowed but not completely stopped/reversed

154
Q

The inflammation phase of ILDs offers a window of opportunity for treatment. How can the transition between inflammatory and fibrotic phases be detected? What is the disadvantage of this.

A

Fibrosis can only be detected through a decline in lung function, which occurs ~6 months after initiation of the fibrotic phase

155
Q

What is a hypersensitivity pneumonitis?

A

Exposure-related pneumonitis, occuring in susceptible/sensitized individuals to inhaled environmental antigens

156
Q

When does acute hypersensitivity pneumonitis occur, and when does chronic hypersensitivity pneumonitis occur?

A

Acute: intermittent high-level exposure to antigens
Chronic: chronic low-level exposure to antigens

157
Q

True or false: most hypersensitivity pneumonitis become fibrotic

A

False; most remain stable non-fibrotic

158
Q

How can hypersensitivity pneumonitis patients be effectively helped?

A

Removal of causative antigen exposure

159
Q

Which characteristics are shared by auto-immune diseases that cause ILD? (3)

A
  1. Lead to endothelial and epithelial activation & damage
  2. Auto-antibodies are associated with disease progression
  3. Different patterns of ILD, depending on underlying disease
160
Q

How can auto-immune mediated ILD be exacerbated?

A

Environmental triggers (allergens, infections, etc.)

161
Q

What is the chance that auto-immune processes affecting the lungs become fibrotic?

A

40-50%

162
Q

True or false: a big portion of sarcoidosis patients become fibrotic

A

False; fibrosis rarely occurs in sarcoidosis. The reason why sarcoidosis still constitutes a major part of ILD is that fibrosis is far more common than other types of ILD

163
Q

What is the chance that a patient suffering from idiopathic pulmonary fibrosis becomes fibrotic?

A

100%

164
Q

The type of T-cell response is related to fibrosis. Which kind of T-cell responses often turn fibrotic?

A

Th2, Th17

165
Q

Why do Th1-mediated diseases rarely become fibrotic?

A

IFN-γ, a major Th1-cytokine, is anti-fibrotic and inhibits profibrotic Th2-cells

166
Q

What happens to the T-cells of sarcoidosis patients that become fibrotic?

A

They switch to a Th2 type

167
Q

Between which ages does the onset of idiopathic pulmonary fibrosis (IPF) often occur?

A

50-70 years

168
Q

What are common characteristics of IPF patients? (3)

A
  1. Predominantly men
  2. Often (ex) heavy smokers
  3. Genetic predisposition
169
Q

What is the prognosis of IPF without vs. with treatment?

A

Without treatment: 3-5 years
Treatment delays by ~2 years

170
Q

Why is IPF especially difficult to treat?

A

No inflammatory phase, immediately starts with fibrosis

171
Q

What is the hypothesis as to the cause of IPF?

A

Chronic injury of type II pneumocytes leading to their apoptosis, resulting in permanently disturbed epithelial homeostasis

172
Q

What causes chronic injury of type II pneumocytes, leading to IPF?

A

Smoking or environmental irritants

173
Q

Which pathological processes occur in type II pneumocytes in IPF, leading to their apoptosis? (3)

A
  1. Disturbed folding and processing of surfactant proteins
  2. Impaired DNA repair
  3. Maladaptive endoplasmic reticulum stress responses
174
Q

What triggers fibroblast activation and ECM production in IPF?

A

TGF-β/Smad-signaling

175
Q

How many % of IPF-patients have an identified genetic susceptibility locus?

A

~50%

176
Q

Which 3 groups of genes are often related to IPF? (3)

A
  1. Genes involved in telomere biology
  2. Genes involved in surfactant metabolism
  3. Genes involved in mucus function
177
Q

Why are mutations in genes involved in telomere biology often associated with IPF?

A

Telomeres protect against the degradation of chromosomes by restoring the telomeres. Disruption of this process leads to cellular senescence of type II pneumocytes

178
Q

Which phenotypic changes occur in type II pneumocytes that go into senescence (due to disrupted telomere biology)?

A

Pro-inflammatory and profibrotic phenotypic changes -> SASP-cells

179
Q

Why is cellular senescence often a beneficial principle?

A

It stops division of cells that often have DNA damage, thus preventing formation of tumours

180
Q

Which cells should normally clear senescent cells? Why does this not happen with SASP-cells in IPF?

A

NK-cells -> disturbances in NK-cell biology are also related to IPF

181
Q

True or false: reduced telomere length is a predictor of good prognosis in IPF

A

False; reduced telomere length is a predictor of poor outcomes

182
Q

What is surfactant?

A

Mixture of lipids and proteins produced by type II pneumocytes, with the aim of decreasing surface tension in the lungs

183
Q

What happens when surfactant production is inadequate? (2)

A
  1. Epithelial stress
  2. Disturbed barrier function
184
Q

Why do IPF-patients often have a high bacterial load?

A

Dysfunctional surfactant production leads for disturbed barrier function, allowing the entry of bacteria

185
Q

Which innate cells are involved in a profibrotic role in IPF? (5)

A
  1. Neutrophils
  2. M2 macrophages
  3. ILC2s
  4. Mast cells
  5. DCs (possibly)
186
Q

Which innate cell type has an anti-fibrotic function in healthy situation, but becomes profibrotic when its biology is disturbed?

A

NK-cells

187
Q

Which cells of the adaptive immune system can contribute to fibrosis in IPF? (3)

A
  1. Th2
  2. Th17
  3. B-cells
188
Q

Which cells of the adaptive immune system can lessen fibrosis in IPF?

A

Tregs

189
Q

Why are clinicians hesitant to use immunosuppression in IPF?

A

Trial showed poor outcomes of immunosuppressive regimens in these patients

190
Q

Why does anti-bacterial treatment not benefit IPF-patients? (2)

A
  1. Antimicrobial treatment does not stop pro-inflammatory immune response
  2. Bacterial infection had already induced tissue damage
191
Q

True or false: bacterial infections don’t influence progression of IPF

A

False; bacterial infections exacerbate fibrotic processes

192
Q

What is high bacterial burden in the lower airways in IPF-patients associated with?

A

Rapidly progressive IPF -> higher mortality

193
Q

Which type of treatments is somewhat effective in IPF?

A

Antifibrotic drugs

194
Q

Which two antifibrotics are available for use in IPF?

A
  1. Nintedanib
  2. Pirfenodone
195
Q

What is the mechanism of action of nintedanib?

A

Tyrosine kinase inhibitor -> anti-FGF, anti-PDGF, anti-VEGF

196
Q

In which diseases can nintedanib be used?

A

IPF and other types of ILD that progress to pulmonary fibrosis

197
Q

Why could the use of nintedanib also be useful in the inflammatory stage of ILDs?

A

It could block TCR/BCR signaling, halting inflammation

198
Q

What is the mechanism of action of pirfenodone?

A

Pleitropic anti-inflammatory, anti-fibrotic and anti-oxidative stress function

199
Q

In which diseases can pirfenodone be used?

A

Only in IPF

200
Q

What is the downside of the use of fibrosis inhibitors in IPF?

A

Severe side effects, negatively impacting quality of life

I&I WC1 (20 decks)

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