Respiratory Flashcards
(131 cards)
1
Q
Alpha-1-antitripsin deficiency is caused by a mutation in which gene?
A
SERPINA1 - AAT is part of a group of protein’s known as serine protease inhibitors. Mutations is genes for other proteins in this group, known collectively as serpinopathies, have been implicated in diseases in other organ systems.
2
Q
Alpha-1 antitrypsin inhibits 4 enzymes. Deficiency of AAT is thought to lead to emphysema due to reduced inhibition of which enzyme produced by neutrophils in the lungs?
A
Elastase. Released by neutrophils, in the absence of AAT, damages the elastin in alveoli leading to emphysema.
AAT also inhibits trypsin, chymotrypsin and thrombin.
3
Q
Alpha-1 antitrypsin deficiency has what inheritance pattern?
A
Autosomal codominant. Both alleles produce active protein and play a role in disease severity.
4
Q
What SERPINA1 genotype is most likely to be present in a patient with phenotypic Alpha-1 antitrypsin deficiency?
A
PI*ZZ homozygotes. PI = protease inhibitor. Z = most common disease associated allele. M = normal allele. S is another abnormal allele, but not always associated with disease phenotype. SZ allele develop emphysema if they smoke. MZ allele heterozygotes may have an increased risk of COPD if they smoke but this is controversial.
5
Q
What is the mechanism of liver disease in people with Alpha-1 antitrypsin deficiency?
A
Accumulation of pathological varieties of Alpha-1 antitrypsin in hepatocytes leading to cell death and hepatic inflammation.
6
Q
What are the three classical features of Birt-Hogg-Dubé syndrome? And what is responsible for mortality in these pts most commonly?
A
Skin hamartomas (usually on head and neck), pulmonary cysts, and spontaneous pneumothorax usually before aged 40. It’s and autosomal dominant disease caused by mutations in the folliculin gene. Renal cancer affects 1/3 pts before 50 and is the leading cause of mortality in BHD pts. Regular surveillance is required.
7
Q
What is lymphangioleiomyomatosis, what gene is it associated with, and how does it typically present? What is its plasma marker?
A
Multi system neoplastic disease. Most commonly associated with tuberous sclerosis (germline mutation in TSC gene), but also occurs spontaneously in women aged 30-40 most commonly. Pathogenesis is incompletely understood, but sees abnormal proliferation of smooth muscle like cells systemically a partially oestrogen dependent process. Classical clinical features are chylous pleural effusion, spontaneous pneumothorax and dyspnoea. Chest imaging sees pulmonary cysts. VEGF-D is a plasma marker that delineates it from other cystic lung disease.
8
Q
What is catamenial pneumothorax?
A
Pneumothorax secondary to thoracic endometriosis.
9
Q
What is the most common type of amiodarone induced lung toxicity?
A
Interstitial pneumonitis.
10
Q
How long after commencing amiodarone does amiodarone induced interstitial pneumonitis usually have its onset? How does it present?
A
Almost exclusively >2 months on the medication, and usually 6-12 months after commencement. Usual presentation is insidious non-productive cough, fever, pleuritc chest pain, weight loss. Sometimes have raised crp, esr, WCC. Imaging can look like atypical pneumonia. Restrictive PFTS with impaired DLCO. Foam cells on BAL.
11
Q
How does amiodarone induced organising pneumonia (formerly bronchiolitis obliterans organising pneumonia - BOOP) present?
A
Presents over weeks to months - more acutely than interstitial pneumonitis - with
non-productive cough, fever, dyspnoea, almost always raised inflammatory markers, CXR consistent with pneumonia. However, biopsy demonstrates excessive granulation tissue comprised of fibroblasts and myofubroblasts +/- lymphoid tissue.
12
Q
Draw the lung capacities.
A
See diagram
13
Q
Which zone of the lungs has the highest V/Q ratio?
A
Upper zone
14
Q
Which zone of the lungs has the smallest alveoli?
A
Lower zone
15
Q
Which zone of the lungs has the greatest ventilation?
A
Lower zone
16
Q
Which zone of the lungs has the highest perfusion?
A
Lower zone
17
Q
Which zone of the lungs has the lowest V/Q ratio?
A
The lower zone.
18
Q
What are the components of functional residual capacity?
A
Experiratory reserve volume (ERV) and residual volume (RV).
19
Q
What are the four components of lung volume?
A
Inspiratory reserve volume, tidal volume, expiratory reserve volume and residual volume.
20
Q
What is vital capacity?
A
Inspiratory reserves volume, tidal volume and expiratory reserve volume.
21
Q
What anatomical component of airways contributes most to resistance?
A
Bronchioles. Not alveoli.
22
Q
What are the three defining features of asthma?
A
Variable airway obstruction, bronchial hypersensitivity, airway inflammation
23
Q
What is the definition reversible airway obstruction on PFT?
A
Traditionally, FEV1 or FVC improvement of 12% AND 200mls 10-15mins post bronchodilation. However the latest European guidelines use a flat FEV1 or FVC increase of 10%.
24
Q
How can you demonstrate for airway inflammation when trying to diagnose allergic asthma?
A
Measuring exhaled nitric oxide or measuring peripheral oesinophils are both valid ways of detecting inflammation in allergic asthma.
25
What are radiologists talking about when they say "tree in bud appearance"?
In conditions causing infective or inflammatory changes within the small bronchioles, the peripheral lung parenchymas takes on the appearance of a tree that is 'in bud' - that is a tree that has not yet flowered, but is covered in flower buds at its peripheries. Any number of infections can cause this appearance, but important non-infective causes include Sjogren's disease and rheumatoid arthritis.
26
How can you tell if someone has bronchiectasis on CT scan?
Best recognised method is to compare the diameter of the peripheral airways to their paired vascultare. If the airwas wider than its accomanying vasculature, this indicates radiological bronchiectasis.
27
What is theophylline? How does it work? Why might you use it? What are its issues?
Theophylline is a phosphodiesterase inhibitor which leads to smooth muscle bronchodilation. It also inhibits the binding of adenosine to adenosine receptors on mast cells which reduces their probability of degranulating.
It is usually used when asthma patients on maximal inhaled corticosteroids are still symptomatic. It has a very narrow therapeutic window and its adverse effects are: cardiac dysrhythmia, seizures, and GI upset. It's metabolised by liver P450 enzymes and its plasma levels are volatile during viral infections, liver impairment, or with drugs metabolised by the same enzymes - e.g. anticonvulsants.
28
How do Mepolizumab and Benralizumab is used to treat asthma. How does it work?
IL-5 and IL-5 receptor alpha antagonists respectivley. IL-5 is prodcued by Th2 cells and functions to recruit eosinophils as a chemoattractant. It also activates eosinophils in higher concentrations at sites that is produced. In eosinophilic asthma, eosinophils directly cause harm to the airways, so mepolizumab (anti-IL-5), and also benralizumab (anti-IL-5 receptor alpha ab) impair eosinophil function to treat moderate to severe asthma. Benralizumab leads to antibody-mediated cytotoxic cell death as it is an IgG1 based ab that binds to eosinophil IL-5 receptors. Patients included in the trials had peripheral plasma eosinophil counts of 150-300 cells/ml.
29
Dupilumab is used to treat atopic dermatits and asthma in Australia. How does it work?
Dupilumab is an anti-IL-4 receptor alpha monoclonal antibodiy. The IL-4 receptor alpha domain is a commone to the IL-4 receptor and the IL-13 receptor, and so Dupilumab blocks the effects of both. IL-4 is necessary for the differentiation of naive T cells into Th2 cells that drive the innappropriate allergic response seen in asthma. IL-13 stimulates the production of more goblet cells in epithelial layers, increases mucosal layer turnover, and recruits mast cells and M2 macrophages (those specialised to attack helminths). As with mepolizumab and benralizumab, asthma treatment relies on evidence that the disease is driven by eosinophils.
30
What are the urinary antigen tests that can be done for patients with suspected pneumonia?
Urinary legionella antigen and urinary streptococcus pneumoniae. More sensitive than blood and sputum cultures but remain highly specific.
31
How is cystic fibrosis inherited?
Autosomal recessive
32
What's the name of the newborn test that screens for CF called?
Immunoreactive trypsinogen level. If increased, this is suggestive of CF. Trypsinogen is usually produced by the pancrease and excreted by pancreativ exocrine cells, however in patients with cystic fibrosis, pancreatic exocrine secretion is imparied leading raised trypinsogen levels in the blood.
33
How does the sweat test work for cystic fibrosis diagnosis?
Sweat with low chloride levels is considered diagnosistic for cystic fibrosis due to CFTR mutation impairing chloride secretion.
34
Which condition at birth is most commonly asscoaited with cystic fibrosis?
Meconium ileus
35
What ethnicity is most commonly associated with cystic fibrosis?
Caucasian. Approximately 1 in 28 white people carry a CFTR pathogenic variant. 1 in 3000 are born with cystic fibrosis.
36
What is class I CFTR mutation?
no functional CFTR mutations is made.
37
What is a class II CFTR mutation?
CFTR protein is made but it is mis-folded and is not trafficed to the cell surface correctly. This is the most common cause for cystic fibrosis, and the F508del mutation is the most common single mutation cause of cysitic firbosis impactin 80-90% of CF patients.
38
What is a class III CFTR mutation?
CFTR protein is formed into a channel but it does not open (e.g. G551D). Note that this is a significant mutation as the medication Ivacaftor (Kalydeco) opens the channel in G551D mutations.
39
What is a class IV CFTR mutation?
CFTR protein is formed into a channel but chloride ions doe not cross the channel properly.
40
What is a class V CFTR mutation?
CFTR is made properly, but not in sufficient quantities for it to perform its role.
41
What is a class VI CFTR mutation?
CFTR protein is made and is functional, but is not stable on the cell surface.
42
How does ivacaftor work in the treatment of cystic fibrosis?
Ivacaftor is a 'potentiator' that stabilises the CFTR protein and enables it to open properly. It is used in Class II (in combination with drug to transport the CFTR to the cell membrane), III, and IV disease. There are at least 95 genetic subtypes of that ivacaftor has been shown to be effective for treating. It is as part of dual of triple therapy in the treatmnet of class II mutations (where the CFTR protein is misfolded and doesn't traffic to the cell surface).
43
How do lumacaftor and tezacaftor, and elexacaftor work for cystic fibrosis patients?
Tezacaftor/ivacaftor, tezacaftro/elexacaftor/ivacaftor and lumacaftor/ivacaftor combinations are used to treat F508del patients in combination. Lumacaftor, elexacaftor and texacaftor all work to transport the CFTR protein to the cell membrane. The ivacaftor then stabilises the CFTR protein and allows it to open and function correctly.
44
What is dornase?
Dornase is recombinant human DNAse that breaks down DNA left over from inflammatory cells in the airways. It's inhaled alongside hypertonic saline to assist with clearance of airway secretions.
45
What treatments in CF, apart from the -caftor medications, have been shown to improve lung function?
Inhaled dornase daily, inhaled hypertonic saline daily, inhaled antibiotics (aztreonam or tobramycin) if the pt is colonised with pseudomonas, alternate daily pred dose in pts >18yo, daily macrolide use, ibuprofen (between age 6-18), lung transplantation (advanced CF). Notably, staphylococcal infection prophylaxis has not demonstrated lung function improvement.
46
What are the criteria for lung tranplantation in patients with CF?
FEV1 less than 35%. Increased IV abx use for exacerbations. PO2 less than 60mmHg. PCO2 greater than 50mmHg. Clinical organism resistance. Impaired quality of life.
47
What anatomical variant leads to infertility in men with cystic fibrosis?
Absent vas deferens
48
What is the aetiology of disease in patients with group 1 pulmonary hypertension?
These patients are said to have pulmonary arterial hypertension (pre-capillary pressure is raised). This can occur secondary to medications, connective tissue disease, or inherited causes. It can also be idiopathic.
49
What is the aetiology of group 2 pulmonary hypertension? What pattern of hypertension is seen?
This is caused by left heart failure. Increased pressures will be seen in the post-capillary vessels.
50
What is group 3 pulmonary hypertension?
This group is the result of chronic lung diseases and hypoxaemia.
51
What is group 4 pulmonary hypertension the result of?
Group 4 pulmonary hypertension is the result of chronic pulmonary artery obstrcuction aka CTEPH.
52
What is group 5 pulmonary hypertesnion?
This is hypertension secondary to unclear causes.
53
What are the classic clinical features of pulmonary hypertension?
Dyspnoea and fatigue are the most common and earliest symptoms. They are due to an inadequate increase in cardiac output during exertion. As PH continues, right heart failure and its symptoms begin. This includes exertional chest pan, syncope, peripheral oedema, abdominal pain and anorexia due to GI oedema.
54
What are the classic exam findings for pulmonary hypertesnion that is causing cardiac abnormalities?
Elevated JVP. Early in the disease a prominent 'a' wave is seen, and later a prominent 'v' wave may be seen if tricuspid regurgitation has developed. The precordial findings are:
-right sided third or fourth heart sounds associated with
-a left parasternal heave or a downward subxiphoid thrust consistent with RV hypertrophy
-a holosystolic murmur (heard throughout systole), consistent with tricuspid regurgitation
Don't forget to palpate the liver - hepatomegaly, a tender liver, or a pulsatile liver are all consistent with RV failure.
55
What is the definitive treatment for CTEPH
Pulmonary endarterectomy
56
What is acute eosinophilic pneumonia?
Presents as rapidly progessive respiratory failure with cough and fever. Thought to be an immune response to an inhaled allergen. Risk facotrs: new smoking behaviour, exposure to fine dust particles, second hand smoke exposure. Radiographically AEP presents with bilateral peripheral ground glass infiltrates seen apically. Usually diagnosed on BAL - eosinophils. Treatment is steroids.
57
What is allergic bronchopulmonary aspergillosis (ABPA)? What are the diagnostic tests for it in asthma?
IgE-mediated reacction in the lungs in a person sensitised to aspergillus fumigatus. Diagnostic criteria - at a minimum must have asthma, proximal bronchiectasis, immediate cutaneous reactivity to aspergillus species, elevated total serum IgE (>1000), elevated serum specific IgE/IgG to A fumigatus (or same other species responsible for positive on skin testing).
58
What is the natural hisotyr of ABPA?
5 stages. Stage 1 - acute fever, cough, pain, haemoptysis, sputum (elevated Ige). Stage 2- remission with stable asthma (normal IgE). Stage 3 - exacerbations (marked IgE elevation). Stage 4 - corticosteroid - dependent asthma. Elevated to normal IgE. Stage 5 - cyasnosis, fibrtotic lungs (possible cavitations), normal IgE.
59
What is the treatment for ABPA?
During exacerbations or initial acute episode - steroids +/- azole to treat aspergillus. Can drop the azole (itraconazole - if fails voriconazole) whilst in remission, but may need it again during other stages.
60
What type of orgnanism are legionella subspecies?
The are aerobic intracellular gram negative bacilli. L. longbeachae is the most common cause of human disease in Australia, however L. pneumophilia is more common elsewhere. These species cause pnuemonia. Rarely, extrapulmonary infection occurs. The other subspecies are more often assocaited with extrapulmonary disease. They live in soil and water. Person to person contact generally does not occur.
61
What clinical features might make you suspect an atypical organism is responsible for a pneumonia infection?
LFT derangement, nausea, vomiting, diarrhoea
62
What is the first line treatment for massive haemoptysis?
Bronchial artery embolisation. Small studies have shows that tranexamic acid may be succesful in pts with small bleeds who have CF.
63
What are the three subtypes of mesothelioma?
Epithelioid, sarcomatoid and biphasic (mixed between the other two). Epithelioid mesotherlioma is the most common (60%) subtype and is asscoaited with better prognosis.
64
How is mesothelioma diagnosed?
Biopsy of pleura or other surface affected. This needs to be done via VATS as pleural fluid usually only has a diagnostic yield of ~30%.
65
What are the poor prognostic markers for mesothelioma?
Sarcomatoid subtype, poor ECOG, male, weight loss, chest pain, high PET uptake, expression of COX-2, expression of VEGF, hypermethylation of the P16 (INK4a) gene, and high serum mesthelin levels.
66
Does radiation work in the treatment of mesothelioma?
No.
67
What systemic therapy is available for mesotheloma?
First line ipi/nivolumab is standard of care. Phase three tiral in 2021 demonstrated superior to the previous standard of care combine chemotherapy.
68
How should pleural effusion be managed in the setting of pleaural mesothelioma?
Talc pleurodesis with VATs guidance works best. Tunnel catheters can also work.
69
What paraneoplastic antibody is associated with narcolepsy?
Anti-Ma
70
What is the HLA haplotype associated with narcolepsy?
HLA-DQB1 0602. Seen in 40% of patients with narcolepsy without cataplexy, and 90% of patients with narcolepsy with cataplexy. Background population has 25% prevalence of this haplotype.
71
Narcolepsy with cataplexy is likely due to destruction of cells in the brain through an autoimmune process. What chemical do these cells normally produce that is critical for a normal sleep wake cycle and is lost in narcolepsy with cataplexy?
Orexin (AKA hypocretin)
72
What is cataplexy?
Sudden onset generalised muscle weakness leading to partial or complete collapse. Classically triggered by laughter, excitement or anger. Speech may be impaired, vision blurred, and respiration irregular during an attack. Can rarely manifest as status catapleticus- lasting hours. Patients often fall asleep after a cataplectic attack.
73
What's a hypnagogic hallucination? (associated with narcolepsy)
visual or auditory perceptions on falling asleep
74
What's a hypnopompic hallucination? (associated with narcolepsy)
visual or auditory perceptions on awakening
75
What is the classic narcolepsy tetrad?
Excessive daytime sleepiness, cataplexy, sleep paralysis and sleep-adjacent hallucinations (hypnagogic and hypnopompic)
76
What investigations are required for the diagnosis of narcolepsy?
Polysomnography and multiple sleep latency testing. Polysomnography identifies the quality of sleep prior to doing the sleep latency test, as there may be confounders that are making the patient sleepy (e.g. OSA, REM sleep disorder etc)
77
What is a multiple sleep latency test? What is found to aid the diagnosis of narcolepsy?
If polysomnography the night before shows a >6hrs of sleep the an MSLT can be done. The MSLT measures how long it takes the patient to fall asleep during the day in a dark room. If there are greater than or equal to 3 sleep-onset REM periods (REM sleep being acheived within 15mins of sleep, normal is ~90mins into sleep), and a mean sleep latency of <5minutes, this is specific (but insensitive) to narcolepsy. Normal subjects fall asleep in 10 to 15mins.
78
What will be low in the CSF of patients with narcolepsy with cataplexy?
Orexin (hypcretin)
79
What pharmacotherapy is available for the treatment of excessive daytime sleepiness in in narcolepsy?
First line: modafinil, pitolisant, sodium oxybate, solriamfetol. Pitolisant is tolerated the best.
80
What should be done for a patient in COPD related hypercapnoeic respiratory failure on NIV who is unable to adequately clear their secreations?
Intubate. Other reasons for intubation - failure to improve respiratory acidosis, failure to improve O2, failure to reduce CO2, persistent cadiac arryhtmia, haemodynamic instability, impaired conciousness or agitation, after complete respiratory arrest, vomiting
81
Does CPAP reduce the risk of cardiovascular events in patients with OSA?
No. SAVE trial showed that in patients with moderate to severe OSA, CPAP did not reduce mortality, cardiovascular events. It did, however, significantly reduce snoring, and improve quality of life and mood.
82
In polysomnography, what's the definition of apnoea?
90% cessation for more than 10s of sleep despite ventilatory effort
83
In polysomnography, what's the definition of a hypopnoea?
Reduction in airflow by more than 30% with concurrent reduction in oxyhaemoglobin saturation by at least 3% or arrousals from sleep.
84
What is the AHI with regard to polysomnography?
The apnoea/hypopnoea index is a measure of the number of apnoea/hypopnoea events per 1 hr of sleep. AHI of 5-15 is conseidered mild, 16-30 is moderate, and >30 is severe OSA.
85
What AHI numbers should be observed to before considering treatment with CPAP?
AHI >15, or AHI 5-14 with symptoms suggestive of OSA on top of other associated comorbidities like stroke, IHD. For pts who don't meet CPAP criteria, they may benefit from avoiding supine sleep, mandibular advancement devices, surgery, or life style modification.
86
What occupational exposure increases risk of contracting TB infection, and progression of TB disease in the lungs?
Silicosis. In addition, silica exposure even in the absence of silicosis is enough to increase tuberculosis risk. Further, silica exposure is associated with higher risk of COPD, malignancies, mycobacterial, fungal and bacterial lung infections.
87
What occupational exposure causes a non-caseating granulomatous pneumoconiosis that is indistinguishable clinically from sarcoidosis?
Beryllium exposure. Seen in people who in the aerospace of copper mining industries.
88
What is byssinosis?
A progressive respiratory disease charterised by cough, shortness of breathm, chest tightness and airflow obstruction, most commonly caused by excessive exposure to fibres in patients who work in the cotton industry.
89
What industry exposure classically causes emphysema with nodular fibrosis?
Coal miners pneumoconiosis.
90
Can a person hold a licence if their AHI is >30 and they don't use a CPAP machine?
No. This patient would be defined as having severe OSA. They are only allowed to hold a liscence if they agree to treatment, are compliant with treatmnet, and the response to treatment is satisfactory as demonstrated by objective measures.
91
What factors shift the O2 dissociation curve to the right (i.e. cause O2 to dissociated more easily from haemoglobin to perfuse tissue)
Lower concentrations of haemoglobin, high partial pressure of CO2, lower pH, higher temperature, increased concentrations of 2,3 diphosphoglycerate (2,3-DPG).
92
What is 2,3 diphosphoglycerate? (2,3-DPG)
An intermediate meabolite in the glycolytic pathway which binds to haemoglobin in red blood cells and stabilises the 'T-state' which decreases its affinity for oxygen. This allows the Hb to release its oxygen into the tissues. Production of more diphosphoglycerate, as seen in hypoxic states or during exercise, drives the oxygen dissociation curve to the right and maximises O2 delivery to tissue.
93
What are Light's criteria?
Indicate the difference between a transudative and exudative pleural effusion. Pleural fluid is an exudate if any one condition is met: pleural fluid protein to serum protein ratio >0.5. Pleural fluid LDH to serum LDH ratio > 0.6, or pleural fluid LDH more than two-thirds of the upper limit of normal serum LDH.
94
What is the follow-up for incidentally discovered pleural plaques?
Nothing. It's a benign condition. There is a lot of misinformation about pleural plaques from asbestosis exposure - it is not an indicator of progressive disease, it doesn't require follow-up.
95
What is asbestosis?
Pulmonary fibrosis secondary to asbestos exposure. Has a usual interstiail pneumonia pattern of fibrosis.
96
What cancer types are related to asbestos exposure?
Mesothelioma, but also non-small cell lung cancer.
97
What's the best treatment for a tension pneumothorax in hospital?
Chest drain (aka Tube thoracostomy)
98
What are the radiological features of idiopathic pulmonary fibrosis?
Usual interstitial pneumonia pattern (UIP). This is characterised by a gradient from apex to base of peripheral, subpleural reticular opacities, traction bronchiectasis, and honeycombing (3-10mm clustered peripheral cystic airspaces). Ground glass opacities can be found but should be less extensive than raticular abnormalities.
99
What disesases can lead to a usual interstitial pneumonia pattern on CT chest imaging?
Asbestosis, idiopathic pulmonary fibrosis, connective tissue disease.
100
IPF is a progressive lung disease with a poor prognosis and 4 year median survival. What medications have been shown to improve lung function and have a possible mortality benefit?
Nintendinib and pirfenidone - antifibrotic drugs.
101
How dows nintendinib work?
It's a tyrosine kinase inhibitor that targets VEGF, FGF, and Platelet Derived GF receptors.
102
How does pirfenidone work?
By downregulating the expression of procollagen I and III, as well TGF-beta. Both chemicals were demonstrably involved in mouse bleomycin firbosis models, and has translated into humans with IPF.
103
What are the major subtypes of idiopathic interstitial pneumonias?
Idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP), idiopathic nonspecific interstitial pneumnoia (NSIP), respiratory bronchiolitis-interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), and acute intersitial peumonia (AIP).
104
What decades of life does IPF classically present?
6th or 7th. It is the most common of the IIPs.
105
What are the clinical features, the hallmark and chief diagnostic radiographic criterion of for UIP?
Insidious onset, strong male predominence, clubbing, poor progrnosis. Heterogenous appeance with alternating areas of normal lung and interstitial inflammation, firblast foci, and honeycomb change.
106
What is the differential diagnosis for UIP?
IPF, rheumatoid arthritis, systemic sclerosis, chronic hypersensitivity pneumonitis, familial pulmonary fibrosis, Hermansky-Pudlak syndrome (autosomal recessiver lysosomal disease feeturing oculocutaneous albinism and other issue), ANCA-vasculitis and some drug induced pulmonary fibrosis.
107
What are the clinical features of nonspecific interstiail pneumonia?
Second most common idiopathic interstitial pneumonia following usual intersitial pneumonia. Subacute rather than insidious onset, associated with fever in a third of patients. Clubbing is uncommen. Equal in men and women. Significantly better prognosis than IPF: 75% of patients with NSIP will improve. Strongly associated with connective tissue diseases.
108
What are the radiological featuers of NSIP?
Bilateral ground glass opacities involving the lower lobes. Crazy paving with interspersed interlobular and intralublar reicular opacities. Subpleural sparing. Traction bronchiectasis.
109
What is the differential list of causes for non-specific interstitial pneumonia?
Connective tissue diseases including polymyositis - dermatomyositis, rhematoid arthritis, Sjogren disease, systemic sclerosis, anca vasculitis (though UIP is more common), HIV infection, hypersensitivity pneumonitis, drug-associated NSIP (flecainide, amiodarone, methotrexate, crmustine, nitrofurantoin, stains, chlorambuicil), IgG-4 related systemic disease, familial intersitial pneumonia, graft versus host disease.
110
What are the smoking related intersitial pneumonias?
Desquamative intersittial pneumonia (DIP) and respiartory bronchiolitis-associated interstitial lung disease (RB-ILD).
111
What are clinical features of DIP?
Reasonably uncommon. Affects cigarette smokers (>90% of cases smoke) in their 4th or 5th decade of life. Chest XRs are normal in up to 1/5th of patients.
112
What are the radiographic features of DIP?
CXR is often normal. HRCT shows ground glass opacities wihtout the peripheral reticular opacities characteristic of UIP. Numerous mononuclear cells filling the distal airspaces.
113
What is RB-ILD?
Respiratory bronchiolitis associated ILD. Uncommon smoking related ILD. 4th to 5th decade of life. Average cigarette exposure is 30 pack years. Appears as subacute onset of dyspnoea and new or changed cough. Charactersitic HRCT findings are ground glass opacities and centrilobular nodules.
114
What are the acute idiopathic interstitial pneumonias?
Acute interstitial pneumonia and cryptogenic organising pneumonia,
115
What are the clinical features of acute intersitial pneumonia?
Explosive respiratory symptom onset - rapidly progressive respiratory failure associated with diffuse opacisties on CXR. It is associated with fever in 75% of cases. It is not associated with smoking. Most patients are over the age of 40. Treatment is steroids, but mortality is high (>50% in hosptial), and the rest die wihtin 6 months.
116
What is cryptogenic organising pneumonia?
Acute onset idiopathic interstial pneumonia disease. Mimics CAP. Classically appears 5th-6th decade of life. Smoking is not related to it. It's an inflammatory fibroproliferative disases that causes acute alveolar epithelial injury followed by leakage of plasma and formation of fibrin within alveolar lumen. Presents with cough, dyspnoea and unresolving or recurrent pulmonary infiltrates. Common to have leukocytosis.
117
What are the radiographic features of COP?
HRCT shows patchy air-space consolidation, ground glass opacities, small nodular opacities, and bronchial wall thekening with dilation. More common in lower zones and periphery.
118
What diseases are organising pnuemonia often associated with?
Rheumatoid arthritis, SLE, systemic sclerosis. Myositis panels are often sen including anti-PL-7, antio-PL-12, and anti-MDA5 to look for anti-synthetase syndromes. Sometimes eosinophilic pneumonia, haemorrhage, infection or lymphangitic malignancy can appear like an organising pneumonia - these require bronchoscopy and BAL to investigate. Lastly, granulomatous lung disease like tuberculosis, sarcoidosis, berylliosis and hypersensitivity pneumonitis can appear as an oragnising pneumonia.
119
How is COP treated?
Once other causes of organising pneumonia are excluded, it is treated with steroid, followed by a steroid sparing agent - typically azathioprine then MMF.
120
What hormones can be be produced by small cell lung cancer?
Ectopic ADH, ectopic ACTH.
121
What are the classic features of SCLC?
Assocaited with smoking, rapidly progressive, hormone productive, central, mediastinal lyhmpadenopathy. Rapidly responsive to chemotherapy.
122
What is the treatment for extensive stage small cell lung cancer?
PD-1 inhibitor (atezolizumab has the most data) + carboplatin (eGFR scan required) or cisplatin + etoposide. Some evidence for thoracic radiation if there is residual disease after systemic treatment. If there are symptomatic brain mets at diagnosis, then whole brain radiotherapy is used prior to systemic treatment. If the there are no mets, or the mets are absent, WBRT may not be used. Prophylactic radiation in the absence of mets is controversial, but may extend time to brain mets.
123
What is the treatment for limited stage small cell lung cancer?
Carboplatin/etoposide with thoracic and prophylactic cranial irradiation. Unless its stage I or II - theses should be surgically resected followed by chemotherapy. Note that studies are yet to show benefit from the addition of immunotherapy to regimes for limited stage disease, but have shown survival benefit in extesnive disease.
124
What defines limited stage small stage small cell lung cancer?
LS-SCLC is defined as disease that is limited to the ipsilateral hemithorax and regional lymph nodes and can be encompassed in a safe radiotherapy field. Everything else is considered extensive stage small cell lung cancer.
125
What paraneoplastic phemomena are associated with small cell lung cancer and what are their associated antibodies?
Limbic encephalitis (hippocampal, amygdala, hypothalamus, cingulate gyrus and limbic cortex invovlement). Present with acute/subacute behavioural/mood change, cog impairment/memory problems, hypothalamus dysfunction, somnolescnece, random endocrine dysfunction, absence seizures. Most patients have Anti-Hu or CV2/CRMP5 abs.
Paraneoplastic Lambert Eaton Myasthaenic Syndrome. A disease of reduced acetylcholine release from presynaptic nerve terminals. Leads to weakness that improves with ongoing movement. Secondary to anti-voltage gated calcium channels. SCLC expresses very similar VGCCs that allow abs to target them.
126
What three tests on pleural fluid can be used to detect TB?
Adenosine deaminase level (90% sensitive, 85% specific when raised), interferon gamma, or PCR for mycobacterial DNA. Note that pleural fluid culture is infrequently positive (<30%).
127
Should you culture pleural fluid, do a BAL or do a biopsy of the pleura when considering a diagnosis of pleural TB in a patient without a cough?
Pleural biopsy has 65% sensitivity, pleural culture 35%, and BAL is very low unless there is a cough.
128
What is Loffler syndrome?
The transpulmonary passage of helminth larvae. This includes three types of helminths - ascaris (when causing infection, referred to as toxocarisis - not prevelent in Australia), hookworms (only rarely cause an eosinophilic pneumonia), and strongyloides (most common cause).
129
What is pulmonary alveolar proteinosis?
Macrophage dysfunction leads to inabaility to clear sufactants from alveoli leading to respiratory failure. The most common cause as an adult, is an autoimmune version due to anti GM-CSF-antibodies. Otherwise, genetic causes, otherwise secondary to haematological malignancies, exposure to industrial particulates, or after stem cell transplant.
Most patients present with gradually progessive exertional dyspnoea and unproductive cough.
Diagnosis is made on BAL where "periodic acid-Schiff (PAS) positive material" is found (lipoproteinacious material). This exudate is grossly turbid.
130
What treatment can be given for lymphangioleiomyomatosis?
mTOR inhibitors - everolimus or serolimus. Recall that LAM is caused by mutations in TSC1 or TSC2. These genes encode hamartin and tuberin respectively. These proteins interact with the mTOR signalling pathway and are thought to increase smooth muscle production by activiting this pathway inappropriaetly. mTOR inhibitors do, therefore, stabilise the disease but don't reverse it.
131
What is the significance of a positive periodic acid Schiff stain on BAL?
A diagnosis of alveolar proteinosis.
