Pulmonology Flashcards
1
Q
Which anatomical structures are considered part of the upper respiratory tract (URT)? (3)
A
- Nose
- Sinuses
- Pharynx
2
Q
Into which three parts is the pharynx subdivided?
A
- Nasopharynx
- Oropharynx
- Hypopharynx
3
Q
Which anatomical structures are considered part of the lower respiratory tract? (LRT) (4)
A
- Larynx
- Trachea
- Bronchus/bronchioli
- Lung
4
Q
What kind of epithelium can be found in the trachea?
A
Respiratory epithelium -> cilindrical ciliated epithelium
5
Q
What is the shape of cartilage bands in the trachea?
A
C-shaped
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
7
Q
How many generations of branching can be found in the bronchial system?
A
~24
8
Q
Into which two regions can the bronchial system be divided?
A
- Non-respiratory
- Respiratory
9
Q
Which bronchi & bronchioli are part of the non-respiratory bronchial system? (3)
A
- Bronchus
- Segmental bronchioli
- Non-respiratory subsegmental bronchioli
10
Q
What is the size cut-off between a bronchus and a bronchiolius?
A
Bronchus >1 cm, bronchiolus <1 cm
11
Q
Which structures are part of the respiratory bronchial system? (3)
A
- Respiratory subsegmental bronchioli
- Alveolar ducts
- Alveolar sacs
12
Q
Into how many segments is the left/right lung divided?
A
Left = 9
Right = 10
13
Q
Which cell types can be found in the bronchus? (5)
A
- Cylindric ciliated epithelium
- Goblet cells
- Basal cells
- Neuro-endocrine cells
- Club cells
14
Q
What is the function of the cilia of respiratory epithelium?
A
Beat to remove particulate matters from the respiratory tract
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)
16
Q
What is the function of goblet cells?
A
Production of mucin
17
Q
Where is most mucus in the respiratory tract produced?
A
Bronchial glands
18
Q
What is the function of basal cells in the respiratory tract?
A
Stem cells for respiratory epithelium
19
Q
How are basal cells connected to the basal lamina?
A
Hemi-desmosomes
20
Q
What is the function of neuro-endocrine cells in the respiratory tract?
A
Important in the development of the lungs
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
22
Q
How can neuro-endocrine cells be visualized during histology?
A
Immunohistochemical staining
23
Q
In which bronchi can club cells be found?
A
Smaller bronchioles
24
Q
What are the functions of club cells? (4)
A
- Modulation of inflammatory reactions
- Metabolism of inhaled toxic substances
- Surfactant production
- Stem cells for ciliated/mucous cells
25
Squamous epithelial cells [are/are not] present in healthy respiratory tracts
Not present; presence of squamous epithelium = metaplasia
26
Where in the respiratory tract can bronchial glands be found?
Medium-sized bronchioles, large bronchioles & bronchi
27
Why is it harder to move mucus higher up in the respiratory tract, compared to the smaller structures deep in the respiratory tract?
Lower surface area = less cilia to move mucus
28
Which system influences the density of mucus in the respiratory tract?
CFTR ion transporter
29
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.
Hypophase -> less viscous than upper layer, allowing cilia to move
30
What is the functional unit into which the lungs are divided? How is this determined?
Pulmonary acini/primary pulmonary lobule -> this is the area originating from 1 respiratory bronchiole
31
How many alveoli does a pulmonary acinus contain on average?
~2000
32
What is the smallest identifiable component of the lung? How is this determined?
Lobule/secondary pulmonary lobule -> the area originating from 1 terminal bronchiole (=bigger than acinus!)
33
How many acini does a lobule contain?
3-30
34
How are alveoli connected in the lung? What is their physiological function? Why are they important for pathology?
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
35
Which two cell types can be found in the alveoli of the lung?
1. Type I pneumocyte
2. Type II pneumocyte
36
What is the function of type I pneumocytes?
Gas exchange (thin cells that allow for diffusion)
37
What are the functions of type II pneumocytes? (2)
1. Surfactant production
2. Replacement of damaged type I pneumocytes
38
Which type of pneumocyte covers the majority of the surface of the alveoli? How many % of the surface?
Type I pneumocyte, 95%
39
Which is more abundant: type I pneumocyte/type II pneumocyte
Type II pneumocyte (even though type I pneumocytes cover the majority of the surface)
40
In addition to cells, which structure can be found in the alveoli?
Interstitium
41
Which immune cells can be found throughout the alveoli of the lung?
Alveolar macrophages
42
Which staining is used to visualize connective tissues in the lung?
Elastica van Gieson (EvG)
43
What are age-related normal changes of the lungs? (9)
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
44
What makes the lung easy to enter for pathogens? (2)
1. Large interface with the environment
2. Highly vascularized, allowing blood-borne pathogens to enter
45
Which stainings are used to identify bacterial infections of the lung? (3)
1. Gram
2. PAS
3. Ziehl-Neelsen/auramine
46
What do Ziehl-Neelsen/auramine stainings reveal?
Mycobacteria
47
Which stainings are used to identify fungal infections of the lung? (3)
1. PAS/PAS-D
2. Grocott
3. Immunohistochemistry
48
Which staining can be used to identify viral infections of the lung?
Immunohistochemistry
49
What are conditions that predispose for infections of the lung? (4)
1. Impairment of pulmonary defence mechanisms
2. Lowered host resistance
3. Unusually virulent pathogens
4. Being hospitalized
50
Which defence mechanisms are present in the respiratory tract? (4)
1. Clearing mechanisms -> coughing, sneezing
2. Mucociliary apparatus
3. Phagocytic/bactericidal action
4. Oedema/congestion
51
What kind of respiratory infections are often abundant in case of defects of innate/humoral immunity?
Pyogenic infections
52
What kind of respiratory infections are often abundant in case of defects of cellular immunity?
Intracellular organisms & low-virulent organisms
53
Viral pneumonia is often [self-limiting/severe/deadly]
Often self-limiting
54
What often happens when a viral pneumonia becomes very severe?
Bacterial superinfection
55
Into which major groups can viral infections of the respiratory tract be divided? (3)
1. Specific/restricted to respiratory tract
2. Systemic infections involving the lung
3. Opportunistic infections
56
What are viruses targeting the URT? (5)
1. Rhinovirus
2. Coronavirus
3. Influenza virus
4. RSV
5. Adenovirus
57
What are viruses targeting the LRT? (4)
1. Influenza virus
2. RSV
3. Adenovirus
4. Metapneumovirus
58
Systemic infections by which viral families can also cause respiratory symptoms? (3)
1. Herpesviruses
2. Paramyxoviruses
3. Togaviridae
59
True or false: viral respiratory inections can by easily distinguished through histology
False; limited morphological specificity in viral pulmonary infections
60
Which histological pattern is often seen in viral infection of the lung?
Interstitial lymphocytic pattern with diffuse alveolar damage
61
What is sarcoidosis (definition)?
Granulomatous disorder of unkown cause, affecting multiple organs
62
Why is sarcoidosis difficult to diagnose?
It can resemble many other diseases
63
Which locations of sarcoidosis often have most severe complications? (2) Does sarcoidosis often occur in these areas?
1. Heart
2. CNS
Sarcoidosis in these locations is rare
64
Which organs are most often affected by sarcoidosis? (3) What is a common factor between these organs?
1. Lung
2. Skin
3. Eyes
All three exposed to outside air
65
What is the M:F ratio of sarcoidosis?
1:1
66
Men are often affected by sarcoidosis at an [older/younger] age, whereas women are affected [older/younger]
Men = younger
Women = older
67
How many % of sarcoidosis cases resolves itself, and how many % become chronic?
50/50
68
What is an acutely presenting form of sarcoidosis? Where does it often occur?
Löfgrens syndrome, often occurs in Scandinavia
69
What is the prognosis of Löfgrens syndrome?
Good prognosis
70
What is the treatment strategy of low-risk sarcoidosis?
Observe, treat when necessary
71
How many patients within a low-risk group of sarcoidosis go into remission within 2 years?
60-70%
72
What is the treatment strategy of intermediate-risk sarcoidosis?
Treat with low dose glucocorticoids, but try to maintain best quality of life
73
How can treatment of intermediate-risk sarcoidosis be escalated, if needed?
DMARDs or anti-TNF
74
What is the treatment strategy of high-risk sarcoidosis?
Aggressive treatment using high dose corticosteroids with methotrexate
75
What is the hallmark of sarcoidosis?
Granuloma formation
76
What is the structural makeup of a granuloma?
Core of histiocytes (=macrophages), surrounded by fibroblasts & T-cells
77
When do granulomas normally form?
When a foreign object cannot be cleared by the immune system and needs to be encapsulated
78
What is the disadvantage of using anti-inflammatory treatments in case of granulomatous disease?
It could reactivate disease (such as tuberculosis) that is encapsulated in these granulomas
79
What is the antigen causing granuloma formation in sarcoidosis?
Antigen unknown
80
How many % of affected individuals die due to progressive sarcoidosis?
1-5%
81
What are causes of death due to sarcoidosis? (3)
1. CNS involvement
2. Cardial involvement
3. Respiratory failure
82
Which cell type is found in high numbers in BALF of sarcoidosis patients?
Th17.1 cells -> Th17-cells secreting IFN-γ
83
Which cytokine is strongly involved in granuloma formation?
IFN-γ
84
Are the Th17.1 cells found in the BALF of sarcoidosis patients also found in peripheral blood?
No -> increased amount of Th17 cells, but not Th17.1
85
High amounts of Th17-cells in BALF is [favourable/unfavourable] from a prognostic point of view (sarcoidosis)
Unfavourable -> worse prognosis
86
What is an immunological characteristic that can be found in patients with active chronic sarcoidosis >2 years?
Increased numbers of active and naïve T-cells
87
Which activation marker is expressed in high amounts in patients with active chronic sarcoidosis?
CD25
88
CTLA-4 is expressed in [lower/higher] numbers in sarcoidosis patients with worse prognosis. What is the effect of this?
Lower -> less inhibition = more activation, especially on Th17-cells
89
Why can anti-CTLA-4 ICIs provoke sarcoidosis?
They block co-inhibition, sometimes allowing for activation of cells that cause sarcoidosis
90
Which groups of drugs can be used to target sarcoidosis? (2)
1. CTLA4 stimulation
2. Targeting of involved cytokines
91
What are current challenges in sarcoidosis research? (3)
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
What are symptoms of asthma? (3)
1. Shortness of breath
2. Chest tightness/pain
3. Wheezing when exhaling
93
What causes asthma symptoms?
Chronic inflammation of the airways
94
How many people are affected by asthma worldwide? How many deaths/year?
~340 million affected, leading to ~500.000 deaths/year
95
What is the first line clinical management of asthma?
Corticosteroids + bronchodilators
96
What is the mechanism of action of corticosteroids in asthma?
Suppression of pulmonary immune system
97
True or false: all asthma patients respond to corticosteroids
False; this is dependent on disease phenotype
98
What is the downside of the use of corticosteroids in asthma?
Severe side-effects
99
Which class of drugs is used as bronchodilators in asthma? What is their mechanism of action?
β2-agonists, relaxing the smooth muscle cells of the airway wall
100
Why are first line drugs for asthma inhaled?
Local release
101
How many % of asthma patients show no symptom control on first line treatment?
5-15%
102
What is a frequent trigger for asthma exacerbations?
Respiratory infections
103
What are the hallmarks of asthma? (2)
1. Airway hyperresponsiveness
2. Bronchoconstriction
104
What is the result of airway remodelling in asthma?
Narrower airways
105
Which remodelling processes take place in airway remodelling in asthma? (5)
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
True or false: remodelling of the airway in asthma can be reverted with treatment
True and false -> remodelling is partly reversible, but severe remodelling will not be fully restored on treatment
107
What are the processes that constitute an asthma attack?
1. Tightening of smooth muscles
2. Production of mucus
108
What is the underlying mechanisms that triggers an asthma attack?
Mast cell degranulation
109
Mast cell degranulation plays an important role in asthma. Why are anti-histamine therapies not used in asthma? (2)
1. Side effects
2. Only has effect late in asthma pathophysiology -> only works if mast cells are alreay present in the lungs
110
Into which two (immunological) subtypes can asthma roughly be divided? How many % of patients fall into each group?
1. T2-low asthma = 40%
2. T2-high asthma = 60%
111
What are triggers of T2-low asthma?
Non-allergic type -> triggered by smoking or infections
112
What are the main cell types (4) and cytokines (2) involved in T2-low asthma?
Cell types: Th1, Th17, ILC1, ILC3
Cytokines: IFN-γ, IL-17
113
What kind of granulocytes are involved in T2-low asthma?
Neutrophilic inflammation
114
What are triggers of T2-high asthma?
Allergic triggers
115
What are the main cell types (2) and cytokines (4) involved in T2-high asthma?
Cell types: Th2, ILC2
Cytokines: IL-4, IL-5, IL-13, IL-9
116
What kind of granulocytes are involved in T2-high asthma?
Eosinophils
117
What is the effect of IL-4 on B-cells? What does this result in?
Class switch to IgE -> can lead to antigen-specific mast cell degranulation through FcεR
118
Which two arms of activation of asthma-related cells are there in T2-high asthma?
1. Epithelial response leads to damage and activation of epithelial cells
2. Activation of Th2-cells through antigen presentation of allergens by DCs
119
What is the process in which the epithelium drives T2-high asthma? (3 steps)
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
Which alarmins are produced by the epithelium in T2-high asthma when the epithelium is triggered by allergens? (3)
IL-25, IL-33, TSLP
121
What are the effects of IL-4 in T2-high asthma? (3) Some of these are a collaboration between with another cytokine. Which?
1. Class switching to IgE
2. Activation of M2-macrophages (together with IL-13)
3. Recruitment of mast cells (together with IL-9)
122
What are the effects of IL-5 in T2-high asthma? (2)
1. Eosinophil recruitment
2. Increased eosinophil production in bone marrow
123
What is the effect of IL-9 in T2-high asthma? With cytokine contributes to this process?
Recruitment of mast cells, together with IL-4
124
What is the effect of IL-13 in T2-high asthma? (4) Some of these are a collaboration between with another cytokine. Which?
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
Asthma symptoms are ofte more severe [higher up in the gas conduction system/deeper in the lung]. Why?
Higher up in the gas conduction system -> higher amount of harmful substances
126
What defines an innate lymphoid cell?
No expression of lineage markers
127
Which ILC is important in T2-high asthma?
ILC2
128
How are ILC2s activated in T2-high asthma?
Activated by alarmins produced by epithelium (IL-33, IL-25, TSLP)
129
Which epithelial cells produce high amounts of alarmins upon triggering by allergens in T2-high asthma?
Tuft cells -> produce high amounts of IL-25
130
How can ILC2s be stained?
Lineage negative cells that express IL7R and CRTh2
131
How do ILC2s collaborate with Th2-cells in case or strong allergens?
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
What are examples of strong allergens? (2)
Moulds, proteases
133
How do ILC2s collaborate with Th2-cells in case of mild allergens?
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
What is an example of a mild allergen?
House dust mite
135
What are the characteristics of ILC2s involved in activation of Th2-cells in case of a strong allergen?
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
What are the characteristics of ILC2s involved in reactions against milder allergens? (4)
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
Why is it difficult to study the role of ILC2s in T2-high asthma?
Only present in very low numbers in blood and tissue + tissue is hard to obtain
138
What are activation markers of ILCs? Which cell type has the same activation markers?
CD45RA = inactive
CD45RO = active -> produce cytokines upon activation
This is also true for memory T-cells
139
Which cells can be found in increased amounts in blood of T2-high asthma patients? Does this also correlate with disease severity?
CD45RO+ ILC2s (=activated ILC2s)
This correlates with disease severity -> higher numbers = worse
140
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
Worse response in case of high activated ILC2s
141
What is the role of CD8+ T-cells in T2-high asthma? (hypothesis)
Under asthmatic circumstances, CD8+ cells produce type II cytokines instead of IFN-γ -> exacerbates disease
142
What is paradoxical about the fact that CD8+ T-cells can cause asthma excerbations?
CD8+ T-cells normally produce IFN-γ, which should suppress the T2-response leading to asthma
143
Why do CD8+ T-cells that produce type II cytokines respond poorly to treatment?
They are not very sensitive to steroids
144
What are symptoms of interstitial lung diseases? (4)
1. Shortness of breath
2. Fatigue
3. Coughing (in some patients)
4. Respiratory failure
145
What is the only curative treatment for interstitial lung diseases?
Lung transplantation
146
What are major groups of interstitial lung diseases? (4) How many % of ILD patients belong to each group?
1. Sarcoidosis = ~50%
2. Interstitial idiopathic pneumonias = ~20%
3. Auto-immune diseases = ~20%
4. Exposure-related ILD
147
What are the common phases of ILDs? (3)
1. Genetic predisposition & aging as risk factors, environmental factors as a trigger
2. Early phase = inflammation
3. Late phase = fibrosis
148
Where is inflammation located when ILD is triggered by environmental factors in the airways?
Epithelial cells, which become fibrotic
148
Where is inflammation located when ILD is triggered by auto-immune disease?
Endothelium of lung capillaries
149
True or false: fibrotic processes in all kinds of ILD are similar, even if their aetiology differs
True; once the fibrotic phase of ILD starts, this is nearly the same for all ILDs
150
What causes fibrotic processes in ILD? How is it exacerbated?
Recurrent tissue damage causes fibrosis
Fibrosis causes lung tissue to stiffen, leading to additional damage -> in turn increases fibrosis
151
Where in the lung does fibrosis often start in ILD
Subpleural, then spreading throughout the lung
152
True or false: the inflammation phase of ILDs can be dampened/stopped, thus preventing fibrosis from occurring
True; at the inflammatory stage, fibrosis can still be prevented by stopping inflammatory underlying mechanisms
153
True or false: the fibrosis phase of ILDs can be stopped, allowing for the damage to be undone
False; one fibrosis has started, this process can only be slowed but not completely stopped/reversed
154
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.
Fibrosis can only be detected through a decline in lung function, which occurs ~6 months after initiation of the fibrotic phase
155
What is a hypersensitivity pneumonitis?
Exposure-related pneumonitis, occuring in susceptible/sensitized individuals to inhaled environmental antigens
156
When does acute hypersensitivity pneumonitis occur, and when does chronic hypersensitivity pneumonitis occur?
Acute: intermittent high-level exposure to antigens
Chronic: chronic low-level exposure to antigens
157
True or false: most hypersensitivity pneumonitis become fibrotic
False; most remain stable non-fibrotic
158
How can hypersensitivity pneumonitis patients be effectively helped?
Removal of causative antigen exposure
159
Which characteristics are shared by auto-immune diseases that cause ILD? (3)
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
How can auto-immune mediated ILD be exacerbated?
Environmental triggers (allergens, infections, etc.)
161
What is the chance that auto-immune processes affecting the lungs become fibrotic?
40-50%
162
True or false: a big portion of sarcoidosis patients become fibrotic
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
What is the chance that a patient suffering from idiopathic pulmonary fibrosis becomes fibrotic?
100%
164
The type of T-cell response is related to fibrosis. Which kind of T-cell responses often turn fibrotic?
Th2, Th17
165
Why do Th1-mediated diseases rarely become fibrotic?
IFN-γ, a major Th1-cytokine, is anti-fibrotic and inhibits profibrotic Th2-cells
166
What happens to the T-cells of sarcoidosis patients that become fibrotic?
They switch to a Th2 type
167
Between which ages does the onset of idiopathic pulmonary fibrosis (IPF) often occur?
50-70 years
168
What are common characteristics of IPF patients? (3)
1. Predominantly men
2. Often (ex) heavy smokers
3. Genetic predisposition
169
What is the prognosis of IPF without vs. with treatment?
Without treatment: 3-5 years
Treatment delays by ~2 years
170
Why is IPF especially difficult to treat?
No inflammatory phase, immediately starts with fibrosis
171
What is the hypothesis as to the cause of IPF?
Chronic injury of type II pneumocytes leading to their apoptosis, resulting in permanently disturbed epithelial homeostasis
172
What causes chronic injury of type II pneumocytes, leading to IPF?
Smoking or environmental irritants
173
Which pathological processes occur in type II pneumocytes in IPF, leading to their apoptosis? (3)
1. Disturbed folding and processing of surfactant proteins
2. Impaired DNA repair
3. Maladaptive endoplasmic reticulum stress responses
174
What triggers fibroblast activation and ECM production in IPF?
TGF-β/Smad-signaling
175
How many % of IPF-patients have an identified genetic susceptibility locus?
~50%
176
Which 3 groups of genes are often related to IPF? (3)
1. Genes involved in telomere biology
2. Genes involved in surfactant metabolism
3. Genes involved in mucus function
177
Why are mutations in genes involved in telomere biology often associated with IPF?
Telomeres protect against the degradation of chromosomes by restoring the telomeres. Disruption of this process leads to cellular senescence of type II pneumocytes
178
Which phenotypic changes occur in type II pneumocytes that go into senescence (due to disrupted telomere biology)?
Pro-inflammatory and profibrotic phenotypic changes -> SASP-cells
179
Why is cellular senescence often a beneficial principle?
It stops division of cells that often have DNA damage, thus preventing formation of tumours
180
Which cells should normally clear senescent cells? Why does this not happen with SASP-cells in IPF?
NK-cells -> disturbances in NK-cell biology are also related to IPF
181
True or false: reduced telomere length is a predictor of good prognosis in IPF
False; reduced telomere length is a predictor of poor outcomes
182
What is surfactant?
Mixture of lipids and proteins produced by type II pneumocytes, with the aim of decreasing surface tension in the lungs
183
What happens when surfactant production is inadequate? (2)
1. Epithelial stress
2. Disturbed barrier function
184
Why do IPF-patients often have a high bacterial load?
Dysfunctional surfactant production leads for disturbed barrier function, allowing the entry of bacteria
185
Which innate cells are involved in a profibrotic role in IPF? (5)
1. Neutrophils
2. M2 macrophages
3. ILC2s
4. Mast cells
5. DCs (possibly)
186
Which innate cell type has an anti-fibrotic function in healthy situation, but becomes profibrotic when its biology is disturbed?
NK-cells
187
Which cells of the adaptive immune system can contribute to fibrosis in IPF? (3)
1. Th2
2. Th17
3. B-cells
188
Which cells of the adaptive immune system can lessen fibrosis in IPF?
Tregs
189
Why are clinicians hesitant to use immunosuppression in IPF?
Trial showed poor outcomes of immunosuppressive regimens in these patients
190
Why does anti-bacterial treatment not benefit IPF-patients? (2)
1. Antimicrobial treatment does not stop pro-inflammatory immune response
2. Bacterial infection had already induced tissue damage
191
True or false: bacterial infections don't influence progression of IPF
False; bacterial infections exacerbate fibrotic processes
192
What is high bacterial burden in the lower airways in IPF-patients associated with?
Rapidly progressive IPF -> higher mortality
193
Which type of treatments is somewhat effective in IPF?
Antifibrotic drugs
194
Which two antifibrotics are available for use in IPF?
1. Nintedanib
2. Pirfenodone
195
What is the mechanism of action of nintedanib?
Tyrosine kinase inhibitor -> anti-FGF, anti-PDGF, anti-VEGF
196
In which diseases can nintedanib be used?
IPF and other types of ILD that progress to pulmonary fibrosis
197
Why could the use of nintedanib also be useful in the inflammatory stage of ILDs?
It could block TCR/BCR signaling, halting inflammation
198
What is the mechanism of action of pirfenodone?
Pleitropic anti-inflammatory, anti-fibrotic and anti-oxidative stress function
199
In which diseases can pirfenodone be used?
Only in IPF
200
What is the downside of the use of fibrosis inhibitors in IPF?
Severe side effects, negatively impacting quality of life
