Respiratory Flashcards

Question

Causes of hypoxia with normal A-a gradient

Answer 1

1. Alveolar hypoventilation - But these patients have high PaCO2 2. Low PiO2 - When FiO2 \<0.21 or barometric pressure \<760mmHg

Answer 2

* 1 in 2800 live births * 1 in 25 people are asymptomatic carriers of a CF gene mutation * 50% of the CF population were hospitalised at least once in 2003 * Life expectancy is improving

Answer 3

Iva**c**a**ft**o**r** - potentiator * facilitates **opening of Cl-** channel and **improves CFTR activity** * **increases time open** Luma**c**a**ft**o**r -** corrector * Improves **CTFR production/processing** * **puts more in** Tezacaftor combined with Ivacaftor *

Answer 4

* 3 consecutive central respiratory events, separated by the characteristic **crescendo-decrescendo respiratory pattern.** * on average \>5/hour of sleep characteristic apneas or hypopneas must occur * length of each crescendo-decrescendo cycle must be at least **40 seconds** * Longer cycle lengths are associated with more severe cardiac disturbance. * Associated in **CCF, neurologic diseases or use of sedative medications**

Answer 5

* NSCLC - 85% * SCLC - 15% * Remember EGFR and ALK - as have targetted agents

Answer 6

* **Group 1 - Pulmonary arterial HTN (PAH)** * causes: idiopathic, inherited, drugs, CTD (scleroderma, RA, SLE), HIV, portal HTN, CongHD, schistosomiasis * worst survival of all the groups * **Group 2 - PH due to left heart disease** (also have elevated **LA pressure \> 14mmHg**) * causes LV systolic/diastolic dysfunction, Mitral/aortic valve disease * **Group 3 - PH due to chronic lung disease and/or hypoxaemia** * **Group 4 - PH due to chronic thromboembolic disease** * **Group 5 - PH due to unclear multifactorial mechanisms**

Answer 7

Primary spontaneous vs Secondary Spontaneous * **Primary spontaneous**: occurs in the absence of a precipitating event, in a person without known lung disease * **Secondary spontaneous:** all other spontaneous pneumothoracies

Answer 8

* **Mild** - FEV1% predicted **\>70%** * **Moderate** - FEV1% predicted **60 - 69%** * **Moderately Severe** - FEV1%predicted **50 - 59%** * **Severe** - FEV1% predicted **35 - 49%** * **Very severe** - FEV1% predicted **\<35%** * A similar scale can be applied for restrictive defects with FVC substituted

Answer 9

* Combinations of **SABA + SAMA** are more effective compared to either medication alone in improving FEV1 and Sx * **LAMAs\>LABAs** at reducing exacerbaions and decreasing hospitalisation * **LABA + LAMA increases FEV1, reduces Sx and exacs** compared to monotherapy * In **summary combination therapies are more effective** than the individual therapies

Answer 10

* **Poor daytime functioning** - sleepiness and fatigue = increased risk of **accidents** * Psychiatric disorders * **Cardiovascular morbidity -** increased risk of systemic HTN, pulm HTN, CAD, arrhythmias, CCF, stroke * Metabolic syndrome and T2DM * NAFLD * Increased perioperative complications * **Mortality - all cause if severe and untreated**

Answer 11

* Exacerbations of crhonic obstructive pulmonary disease (COPD) that are complicated eby hypercapnic acidosis (PaCO2\> 45mmHg or pH \< 7.30) * Cardiogenic pulmonary oedema * Acute hypoxic respiratory failure

Answer 12

Of note: 1. **SLE -** is LESS likely to cause ILD. More **Pleural or serositis** with **diffuse alveolar damage (DAH)** ie pulmonary haemorrhage 2. **RA** - **UIP** pattern is common 3. **Scleroderma** - **NSIP** pattern is common

Answer 13

1. cardiac or respiratory arrest 2. Inability to cooperate, protect the airway, or clear secretions 3. Severly impaired consciousness 4. Nonrespiratory organ failure that is acutely life threatening 5. Facial surgery, trauma or deformity 6. High aspiration risk 7. prolonged duration of mchanical ventilation anticipated 8. Recent oesophageal anastomosis

Answer 14

* **Continuous pressure** - regardless of whether patient is inspiring or expiring * Generally **5 to 20cmH2O (mmHg if PEEP)**

Answer 15

* HRCT consistent with IPF in ast 12 months * FEV1/FVC \>0.7 - not obstructed * FVC \> 50% * DLCO \> 30% * MULTIDISCIPLINARY DIAGNOSIS * Patient must not have ILD due to other known causes including domestinc and occupational environmental exposures, CTD or drug toxicity * Must by treated by specialist respiratory physician

Answer 16

Type 4 PAH

Answer 17

\*pretty much only antifibronlytics

Answer 18

Enlargement of c**entral pulmonary arteries** with attenuation of peripheral vesels = **oligemic lung fields** Also **RV enlargement** (diministed retrosternal space), **RA dilation** (prominent RH border) **+/- underlying cause = interstitial lung disease**

Answer 19

* **Apnoea - \>90% decrease in airflow compared with preceding signals for \>10 seconds** * **Obstructive** = **continued** respiratory effort throughout event * **Central** = **NO respiratory effort** throughout the event * **Mixed** = **NO respiratory effort** at the start, **followed by respiratory effort** at a later part of the apnoea * **Hypnoea -** **reduction** of airflow to a degree that is insufficient to be called an apnoea * Airflow decreases \>30% but (\<90%) c/f baseline * The diminished airflow lasts \>10 seconds * Associated with either a 3% O2 desat from baseline or an EEG arousal * **RERA (respiratory effort related arousal) -** change in ariflow that is insufficient to be called apnoea or hyponoea * event \>10sec with flattening of the nasal pressure waveform and/or evidence of increased respiratory effort terminating in arousal

Answer 20

* A \>**12% AND \>200mL increase in FEV1 or FVC** is a significant reversible response to bronchodilators * If reversibility is substantial: \>400ml then treat for asthma

Answer 21

* Newborn screening program * heel prick blood test 48 - 72 hours * measures **immunoreactive trypsin (high sens, low spec)** * If elevated samples are tested for **mutations in CFTR gene (but \>2000 mutations)** * homozygous or compound heterozygous mutations = assumed CF * **Sweat test for confirmation (sweat chloride \> 60mmol/L)** * NB: compound heterozygote = 2 different mutant alleles at a particular gene locus * Clinical presentation at birth with **meconium ileus**

Answer 22

* **Pirfenidone -** pleotrophic novel antifibrotic * **ADR**: **GIT** (nausea, diarrhoea, dyspepsia, and vomiting), **photosensitive rash, derranged LFTs** * **Nintendanib -** intracellular TK inhibitor * **ADR: Diarrhoea also nausea**, vomiting and decreased appeptite, d**erranged LFTs. Possible cardiovasculat risk and bleeding risk for those anticoagulated** * contraindicated **if significant IHD** * As per **FVC monitoring (ASCEND, IMPULSIS)** * trials included only patients with mild-mod disease

Answer 23

PaCO2/0.8 = adding a quarter to it

Answer 24

Sinus tachycardia + 1. peaked P waves 2. right axis deviation (S waves in lead I) 3. Tall R waves in lead Vi 4. Right bundle branch block 5. Inverted T waves in lead Vi (normal) spreading across to lead V2 or V3 6. A shift to transition point ot the left, so that the R wave equals ths S wave in lead V5 or V6 rather than in lead V3 or V4 (clockwise rotation). A deep S wave will persist in lead V6 7. Q wave in lead III resembling an inferior infarction

Answer 25

**Signs of RVH or strain** * **Right axis deviation,** * **R wave:** S wave ratio \> 1 in lead V1, * complete or incomplete right BBB * **p pulmonale** (peaked p wave in II)

Answer 26

1. **Sinus disease -** common 2. **Pancreatic disease** * pancreatic insufficiency = 2/3 at birth 25% more during childhood. * 15% remain sufficient = risk of pancreatitis * CF related diabetes = 25% by 20 years, 50% of adults 3. **Meconium ileus** - up to 20% of newborns 4. **Rectal prolapse -** rare (more likely if pancreatic enzyme therapy not done) 5. **Hepatobiliary disease** - common but rarely progressive 6. **Infertility** - \>95% of men most commonly due to **absent vas deferens** (Rx microsurgical epididymal sperm aspiration). **CF women also less fertile than other women** 7. **MSK** * reduced bone mineral content = increased risk of fractures and kyphoscoliosis * CF associated arthropathy - 2 to 9% * hypertrophic osteoarthropathy (uncommon) 5% * aquagenic wrinkling (wrinkling and nodules after immersion in water) - up to 80% 8. **Recurrent VTE** - ?related to long term CVC 9. **Anaemia -** 10% of children, more common with advancing age and declining lung function (Fe deficiency, chronic inflam) 10. **Nephrolithiasis** and neprocalcinosis - common (27 - 92%)

Answer 27

1. Reduced consciousness or collapse 2. Exhaustion 3. Cyanosis 4. O2 saturation \<90% 5. Poor respiratory effort, 6. Soft/absent breath sounds 7. Can't speak

Answer 28

* Female gender * Tall stature in men * Low body weight * Failure to stop smoking

Answer 29

Probabiity of malignancy * Low \<5% * young, less smoking, no prior cancer, small nodule size, regular margins and non-upper lobe * Intermediate (5-65%) * mixture of low and high probability features * High (\>65%) * older, heavy smoking, prior cancer, larger size, irregular margin, upper lobe location

Answer 30

1 week post full resolution

Answer 31

**Autosomal recessive** mutation of **cystic fibrosis transmembrane conductance regulator (CFTR)** protein on **Chromosome 7** * **CFTR regulates Cl + Na channels -** mutations lead to **thickened secretions** * Most common mutation **F508del** AKA **Delta F508** found in **70% Caucasian CF patients** There are categories of CFTR gene mutation * Class I - defective protein production = 2 - 5% of cases worldwide * Class II - defective protein procssing (inc Delta F508) = 70% in USA * Class III - defective regulation * Class IV - defective conduction * Class V - Reduced amounts of functional CFTR

Answer 32

* Terminal bronchioles are the smallest airways without alveoli * **The conducting zone =** anatomical dead space (nil gas exchange), vol 150ml * **Respiratory zone =** where gas exchange occurs, vol 2 - 3L

Answer 33

PaO2 \<55mmHg OR \<60mmHg if end organ disease

Answer 34

**PEARL -** definite UIP does **NOT** need a biopsy

Answer 35

Lung Tx is the only **definitive cure for IPF** - refer all appropriate patients regardless of severity **Indications** 1. Desaturation to \<88% or distance \<250m on 6 min walk test 2. \>50m decline in 6 min walk test distance in 6 months 3. Fall in FVC \>10% or DLCO \>15% during 6 month follow up 4. Pulmonary HTN 5. Hospitalisation for acute exacerbation 6. Respiratory decline 7. Pneumothorax

Answer 36

* **ICS + LABA is more effective than either as monotherapy** at improving lung function, health status and reducing exacerbations * However **regular ICS therapy increases risk of pneumonia** especially if severe disease * **Triple Rx - ICS + LABA + LAMA improves lung functio**n, Sx and health status, reduces exacs compared to to monotherapy * In summary triple therapy is great but **prolonged use of ICS increases risk of pneumonia** * **_Long term PO glucocorticoids have numerous SE an no benefits in stable COPD_** * Have a role in acute exac only * **ICS alone do not modify long-term decline of FEV1 nor mortality in COPD** * ADRs of ICS * PO candidiasis, hoarse voice, skin bruising, pneumonia

Answer 37

Pulmonary Rehab | (no mortality benefit)

Answer 38

* **Indication:** CF with G551D or other gating (Class III) mutation or an R117H mutation of the CFTR gene * **Mechanism of action:** **Improve Cl transport by potentiating CFTR** * Benefits G551D pts: **Reduces number of pulmonary exacerbations, improves FEV1 and weight** * ?Benefits in R117H pts: improved lung function and QoL * Cautions * nil longterm safety data * may cause cataracts in long term use * drug interactions and hepatic metabolism

Answer 39

If clinical suspicion of transudate **-Serum:pleural protein gradient** if **\>31g/L** likely transudate =Serum Protein - Pleural Protein * *If \<31** can do albumin gradient if \>12 most likely transudate * *Ratio \<0.6 is the most senstive for transudate**

Answer 40

Lung volume reduction surgery (LVRS) - reduction pneumoplasty is a surgical technique that involves reducing the lung volume by multiple wedge excision in areas where emphysematous changes are most marked. Typically the amount of tissue resected is 20 to 35 percent of the volume of each lung. LVRS modestly improves spirometry, lung volumes, exercise capcity, dyspnoea and quality of life and may improve long-term survival among highly selected patients. Certain clinical features appear to influence the degree of risk and benefit. Potential complications of LVRS include persistent air leak, intraoperative myocardial infarction, reintubation, prolonged mechanical ventilation, pneumonia, wound infection, arrythmias, DVT, PE and death. Recommend NOT performing LVRS in high-risk patients (FEV1 20% of predicted or less and either a DLCO of 20% predicted or less or homogenous emphysema on CT)

Answer 41

* **Face mask -** greatest physiological improvement, poorly tolerated and difficult to monitor for aspiration * **Nasal mask** - best tolerated, but risk of airleak through mouth * **Oronasal mask is preferred for initial use** - if no benefit trial full face mask

Answer 42

Tetracycline (doxycycline or minocycline) * SE: allergic reaction to ABx --\> respiratory failure Talc * causes severe CP +/- chronic pain, ARDS UTD **prefers tetracyclines** due to similar efficacy and no association with ARDS

Answer 43

Controversy re mechanism of action -likely **non-selective phosphodiesterase inhibitors** eg. Theophylline is metabolised by CYP450 mixed function oxidases Clearance of drug declines with age, many other variables also alter drug metabolism **Improves FEV1 and Sx of breathlessness** ADRs - **toxicity** is dose related (bad because therapeutic levels are very close to toxic levels) Fatal cardiac arrhythmias, grand mal convulsions (irrespective of prior epilepsy Hx), headaches, insomnia, nausea, heartburn (last 4 can occur in therapeutic range) **LOTS of drug interactions**

Answer 44

* COPD - most common, worse COPD = worse risk * CF * Primary or metastatic lung malignancy * Necrotising pneumonia * Lots of others less common

Answer 45

Intracellular inhibitor that targets multiple TKs * Effects * Significant reduction in FVC decline (approx 109ml) aka slows progression * NO change in time to first exacerbation or QOL * ADR * GI upset - 60% diarrhoea, nausea * Similar efficiacy to Pirfenidone * Possible cardiovascular risk * Possible small increase in bleeding risk -avoid in those on anticoagulants

Answer 46

* **More ground glass opacities** * **Less honeycombing** * **Better prognosis** * no subpleura involvement

Answer 47

* *Mech -** recombinant humanised **mAb directed against IgE = reduces** immune system response to allergen exposure * *Indication -** maintence of **mod-severe allergic asthma** in pts Rx with **ICS and with raised serum IgE levels** * *ADR -** thrombocytopenia, bleeding, MSK pain, ?Churg Strauss, anaphylaxis * *AKA - Xolair**

Answer 48

1. Smoking Cessation - also slows decline in FEV1 2. Oxygen Supplementation

Answer 49

* Initial **- Staph. aureus, Haem. influenzae** * During adolescence and adulthood **- pseudomonas aeruginosa** * early pseudomonas is quite sensitive * **later mucoid phenotype develops = biofilm =\> resistance to ABx** * Other * Burkholderia cepacia * Stenotrophomonas maltophilia * Achromobacter xylosoxidans * nTB and fungi

Answer 50

1. **Exudate stage** - diffuse _alveolar damage,_ then after 7 - 10 days 2. **Proliferative stage -** resolution of pulmonary oedema, **proliferation of type II alveolar cells,** squamous metaplasia, interstitial infiltration by myofibroblasts, and early deposition of _collagen_ 3. **Some progress to Fibrotic stage -** _obliteration of normal lung architecture, diffuse fibrosis and cyst formation_

Answer 51

* Airways are infilitrared by * **eosinophils** * Activated **T lymphocytes** * Activated mucosal **mast cells** * There is also * thickening of the basement membrane due to **collagen deposition** in subepithelium * **Hypertrophy of airway smooth muscle** * In fatal asthma * multiple airways occluded by **mucous plugs** * **Airway oedema**

Answer 52

1. Alveolar **injury l**eads to 2. Release of **inflammatory cytokines** (TNF, IL1, IL6, IL8) these 3. Recruit **neutrophils** to the lungs where they become activated and 4. Release **toxic mediators** which 5. Damage **capillary endothelium** and alveolar epithelium which 6. Allows **protein to escape vascular spac**e which 7. **Changes the oncotic gradient** which normally favours resorption of fluid so 8. **Fluid poors into interstitium**, overwhelming lymphatics so 9. **Airspaces fill with blood,** proteinaceous **oedema fluid** and **debris** (and functional surfactant is lost 10. End result = **alveolar collapse = impaired gas exchange,** decreased complaince and increased **pulm artery pressure**

Answer 53

* Mechanism - **reduce inflammation by inhibiting the breakdown of intracellular cAMP** * E**.g. Roflumilast -** reduces moderate and severe exac * ADRs * GIT: Diarrhoea, nausea, reduced appetite --\> LOW, abdo ppain * Other- sleep disturbance, headache, ?depression

Answer 54

* Exact mechanism of action unknown - antifibrotic, antiinflammatory, antioxidant * Regulates TGF B1 and TNF alpha in vitro * Inhibits fibroblast proliferation and collagen synthesis * Reduces cellular and histological markers of fibrosis (animal models) * Effects * 1. **Reduction in decline in FVC** and 6MWT * 2. Improved **progression free surviva**l * NO reduction in dyspnoea scores or death * ADRs * 1. Photosensitivity - must wear sun protective clothing!! * 2. Nausea, diarrhoea * 3. Rash

Answer 55

1. Age \> 50 years 2. Male gender 3. WHO functional class III or IV 4. Failure to improve WHO functional class during Rx 5. RV dysfunction 6. Reduced pulmonary arterial capacitance (SV/pa pulse pressure) 7. Hypocapnia 8. Comorbidities (COPD, DM) 9. PAH associated with CTD 10. SSRI use 11. Low vWF levels 12. Bone morphogenetic protein receptor type 2 BMPR2 mutations

Answer 56

* Patient or time can trigger ventilation * Can independently determine pressure delivered to lungs * If low compliance of lungs = low lung volumes * If high compliance of lungs = high lung volumes

Answer 57

* Patient initiates breaths * Patient gets a specific pressure only on inhalation

Answer 58

* Group 1 (idiopathic/inherited) = no primary therapies * Group 2 (2nd to LH disease) = Rx underlying heart disease * **Group 3 (2nd to lung disease causing hypoxaemia) = Rx undering hypoxia cause and supplemental O2 (mortality benefit)** * Group 4 (2nd of chronic TE of prox/distal pulmonary vasculature) = anticoagulation, surgical thromboendartectomy * Group 5 (2nd to multifactorial) = Rx underlying

Answer 59

1. **Assess severity** (WHO functional classification + echo +/-RHC) * Class I - **no** limitations of physical activity * Class II - **slight** limitation of physical activity, comfortable at rest * Class III - **marked** limitation of physical activity, comfortable at rest * Class IV - inability to complete physical activity without Sx. **Sx at rest** 1. **Primary therapy** - address underlying cause 2. **Advanced therapy -** directed at PH

Answer 60

* Start - recurrent cough which becomes persistent * **recurrent respiratory tract infection due to inability to clear secretions** * chronic infection/inflammation --\> progressive tissue damage in airways * lysosomal enzymes released from infiltrating neutrophils contribute to progressive airway destruction * airway becomes floppy + collapsible under conditions of high flow = air trapping +**airway hyperreactivity**

Answer 61

Normal in newborns Signs of deterioration by **6months** Overtime - develop **obstructive pattern** Lung volumes (TLC and RV) will increase due to **hyperinflation** **FEV1 correlates with survival in CF**

Answer 62

Mean arterial pressure \>25mmHg at rest of pulmonary artery Normal ~ 20mmHg

Answer 63

* Multidisciplinary approach * Optimum benefits achieved from programs lasting 6 - 8 weeks * Supervised exercise training twice weekly is recommended * **Rehabilitation** - shown to be the most effective therapeutic strategy to improve SOB, health status and exercise tolerance * Education alone is not effective

Answer 64

* Large particles - filtered out in the nose * Smaller particles - removed by muco-cillary escalator * Even smaller particles that make it to alveoli - engulfed by macrophages --\> removed via lymphatics/blood flow

Answer 65

Primary spontaneous - SMOKING (biggest) - male gender - cannabis smoking - FHx - Marfans - Homocystinuria - Thoracic endometriosis

Answer 66

**Symptoms** - do not usually occur until pressure 2x normal (50mmHg) * **Initial -** exterional dyspnoea, fatigue (because you can't adequately increase CO during exercise) * **Later** - develop evidence of severe PH with RVF - exertional CP/syncope (when O2 demand goes up), oedema, ascites, pleural effusion **Signs** * **Initial** - increased P2, palpable P2 * **Later -** as RV hypertrophy develops --\> prominent a wave of JVP due to forceful contraction of RA * **Even later** - wider splitting of S2, RV heave. Systolic ejection click, S4, pulmonary ejection murmur * Systemically in very severe disease - tachypnoea, peripheral cyanosis, cold extremities * **Pulse -** small volume (severe disease)

Answer 67

First look at FEV1/FVC * if **\> LLN** then **look at FVC** - if FVC _\>_ LLN = **normal** study, * if **\> LLN** then l**ook at FVC** - if **FVC\< LLN** = **possible restrictive defec**t * if **\< LLN** or **\<0.70** then look at FVC - if **FVC \> LLN** = **obstructive defect** * if **\< LLN** or **\<0.70** then look at FVC - **if FVC \< LLN** = **mixed: obstructive defect with possible restrictive defect or gas trapping** NOTE: post bronchodilator fixed ratio of FEV1/FVC \< 0.70 = COPD type airflow limitation

Answer 68

* Airtrapping: FRC or RV increased \>120% predicted * Hyperventilation: TLC increased \>120%

Answer 69

**_Triple therapy may reduce rate of exac and reduce hospitalisations – for stable COPD patients_** * In patients with a history of exacerbations during the previous year: * Triple therapy with **fluticasone furoate, umeclidinium and vilanterol (ICS/LABA/LAMA)** resulted in: * Lower rate of moderate or severe COPD exacerbations than * Fluticasone furoate–vilanterol (ICS/LABA) or * Umeclidinium–vilanterol (LAMA/LABA) * Lower rate of hospitalisations due to COPD than * Umeclidinium–vilanterol (LAMA/LABA)

Answer 70

* Within 30 days: **Primary graft dysfunction (PGD)** * a form o**f ARDS/**diffuse alveolar damage * After the **first yea**r: Chronic lung **allograft dysfunction (CLAD)** * **bronchiolitis obliterans syndrome (BOS)** or restrictive allograft syndrome * Less but still common at all time points * infection EG bacterial bronchitis/pneumonia, also fungi, CMV, viral and mycobacteria * Less common * malignancy (most common overall: non-melanoma skin cancer, most common after 1 year posttransplant lymphoproliferative disease (PTLD))

Answer 71

There is no conclusive clinical trial evidence that any existing meds for COPD modify long-term decline in lung function

Answer 72

* Mech - **unclear ?sm musc relaxation,** anti-inflam, increase diaphragm contractility, and **CNS stimulation** * Many, many precautions + narrow therapeutic range * **ADR** - nausea, vom, diarhoea, GORD, headache, insomnia, anxiety, tremor * +Rarely **seizures, arrhythmias, tachycardia**

Answer 73

* **Total ventilation** (total volume leaving lung/min) = TV x RR * **Alveolar ventilation** (volume of air **available for gas exchang**e/min) = (TV - **anatomical deadspace**) x RR * **Physiological dead space -** volume of gas that **does not eliminate** CO2 * Anatomical and physiological dead spaces are roughly equal in healthy pts * Physiological increases in lung disease

Answer 74

TNA/Dnase may be an option for patients in whom **standard therapy has failed** and who are not a **candidate for thoracic surgery**

Answer 75

* Weight loss * CPAP * Oral appliances * Upper airway surgery * Hypoglossal nerve stimulation * Devices - nasal splints, expiratory valves, chin straps

Answer 76

* **Type 1 - Oxygenation failure** * Examples: ARDS, Pneumonia, CCF * **Type 2 - Ventilation failure** * Examples: COPD, Asthma

Answer 77

**_UIP - RASH_** 1. **R**eticular abnormality 2. **A**bsence of inconsistent features 3. **S**ubpleural, basal predominance 4. **H**oneycombing with or without traction bronchiectasis

Answer 78

1. **Influenza -** reduces serious illness and death in **COPD** patients 2. 23-valent pneumococcal polysaccharide vaccine **(PPSV23) reduces CAP in COPD pts \<65yrs with FEV1 \<40%** predicted + have comorbidities * In the **general population of adults \>65years** the **13-valent conjugated pneumococcal vaccine (PCV13)** reduces bacteraemia and serious invasive pneumococcal vaccines

Answer 79

* It is the mean forced expiratory flow between the 25% and 75% of the FVC * Reflects flow in smaller, peripheral airways * May be reduced in early obstructive disease

Answer 80

VO2 = maximum rate of oxygen consumption measured during incremental exercise; that is, exercise of increasing intensity.

Answer 81

Soluble Guanylate Cyclase (sGC) Stimulators * Soluble guanylate cyclase (sGC) is an enzyme in the cardiopulmonary system and the receptor for nitric oxide (NO). Pulmonary arterial hypertension (PAH) is associated with endothelial dysfunction, impaired synthesis of NO, and insufficient stimulation of the NO-sGC-cGMP pathway. * eg of GC simulatant riocguat

Answer 82

* *CADET face RIGHT** increased: CO2, Acidity (decreased pH), 2-3 DGP, Exercise, Temperature

Answer 83

No airflow

Answer 84

**BMPR2 -** Bone morphogenetic protein receptor 2 inactivation = **inhibition of vascular proliferation**

Answer 85

Pure obstructive disease with air trapping

Answer 86

No evidence they're an acceptable alternative, shouldn't be used

Answer 87

* Yes, demonstrated in a meta analysis of 13 RCTs * Pneumonia severity index (PSI) 4 and 5 have been shown to most benefit * NNT of 18 to prevent 1 death * **3% reduced mortality, 5% reduced need for mechanical ventilation, LOS reduced by 1 day** Another study IPD **(more thorough review – gold standard)** of the same studies (minus a few that wouldn’t share their data) * More conservative conclusions than Cochrane review regarding benefits of steroids * **No difference in mortality** * **Reduces LOS ~ 1 day** * Reduced time to clinical stability * **Increased hyperglycaemia requiring insulin** * **Increased CAP related readmissions** (NNH 45) **So… steroids in CAP?** * **Not at this stage**

Answer 88

**No for the classic ones, multiple have been tried with no benefit** * methotrexate, cyclosporin, azathioprine, gold, IVIg **Omalizumab** * neutralises circulating IgE without binding to cell-bound IgE * reduces exacerbations in severe asthma, allows lower dose ICS, improves symptom control * requires high IgE levels to qualify * very expensive * may be continued in pregnancy **Mepolizumab/reslizumab** * **anti IL-5** which blocks eosinophil recruitment and activation in steroid resistant eosinophilic asthma * reduces exacerbations 50%, improves FEV1, symptom control, and QOL * requires **peripheral eosinophilia** to qualify **Benralizumab (CALIMA, Lancet Sept 2016)** * anti IL-5r inducing rapid eosinophil depletion * Phase III RCT in those with severe uncontrolled asthma on ICS/LABA with \>=2 exac in last yr and peripheral eos \>300 cell/uL * Improves exacerbation rate, FEV1 **Dupilumab (Wenzel et al, Lancet April 2016)** * anti IL-4r, inhibiting IL-4/13 signalling * Phase IIb RCT in those with uncontrolled asthma already on ICS/LABA * improves FEV1 and reduces exacerbations regardless of baseline eosinophil count

Answer 89

* Aberrant wound healing thought to be the important underlying cause * **Nintedanib and pirfenidone** both **slow disease progression** but don't affect dyspnoea or survival * **Supplemental oxygen** and **pulmonary rehabilitation** improve **QOL**

Answer 90

**Trachea to terminal bronchioles** with predominance in bronchi Mediated by **airway hyperresponsiveness** **Chronic inflammation** punctuated by episodes of **acute inflammation** **Mast cells** * Found in **airway surface in asthmatics**, where none are normally * Initiate **acute bronchoconstrictor** response to allergens or other stimuli * **IgE dependent activation mechanism** * **Histamin**e, prostaglanding D2, cysteinyl leukotreines, other cytokines, chemokines, growth factors **Macrophages/dendritic cells** * Present antigen to uncommitted T lymphocytes * Usually promote TH2 differentiation, require IL-12 or TNFa to differentiate to TH1 * Thymic stromal lymphopoetin instructs dendritic cells to attract TH2 into airways **Eosinophils** * Infiltration a characteristic feature of asthmatic airways * Oxygen derived free radicals and basic proteins drive hyperreactivity * Survive longer by adhering to vascular endothelial walls **Neutrophils** * Increased activated neutrophils may be found in some with severe asthma * Some with mild asthma can have neutrophil predominance **T Lymphocytes** * Coordinate inflammatory response by **recruiitng eosinophils** and **mast cells** with **specific cytokines** * **TH2 phenotype overexpressed** in naive and asthmatic immune system, which **release IL-5 for eosinophilic inflammation** and IL-4/13 for IgE formation * **TH1 predominate in normal airways** * Regulatory **T cells play a role in expression of other cells** **Structural cells** * *May be more important than immune cells in chronic inflammation due to predominance* * Important source of inflammatory mediators

Answer 91

**No** **SAVE study** in Sept 2016 NEJM 45-75yo with mod-sev OSA + coronary or cerebrovascular disease - CPAP + usual care vs usual care alone Primary end point - **death f**rom cardiovascular causes, MI, stroke - **hospitalisation for UA, HF, TIA** AHI decreased from 29.0 -\> 3.7 events per hour in the CPAP group * *No difference in primary endpoint** (1.10; 0.91-1.32) - **significant reduction in snoring and daytime sleepiness - improved health related QOL and mood**

Answer 92

Not necessarily, but is correlated ~23% women ~50% men

Answer 93

* *?Obstruction** - FEV1/FVC \<70% = obstruction * *?Severity** - mild \>70% - mod 60-69% - mod-sev 50-59% - sev 35-49% - very sev \<35% * *?Reversible** - Increase in FEV1 or **FVC \>12% and 200mL** - no SABA for 4hrs, no LABA for 12hrs, no LAMA for \>24hrs prior * *?Inducible** - **Direct** = Metacholin**E** = Sensitiv**E.** Positive if \>20% reduction in FEV1 with \<=4mg/mL - **Indirect =** Mannitol = Specific. Positive if \>15% reduction in FEV1 at \<=635mg cumulative * *- Exercise** = treadmill = **specific and sensitive for exercise induced bronchconstriction but not asthma**. Positive if \>=10% reduction in FEV1 or FVC over any two consecutive time points ``` ?Specific volume loop pattern Variable Extrathoracic (pharynx, larynx, extrathroacic trachea) ```

Answer 94

**?Diffusion** * **DLCO high** = polycythaemia, asthma, increased blood volume, L-\>R shunt, alv haemorrhage * **DLCO low** = thick membrane, decreased surface area, decreased blood volume, decreased lung volume * **DLCO:VA (KCO)** = gas exchange per unit volume. Low in pulm causes, high in extrinsic causes * **DLCO very low** compared with TLC -\> think pulmonary hypertension

Answer 95

Both require imaging and tissue sampling NSCLC staged with TNM - CTCAP first - If mets then no PET. If no mets then PET - PET upstages 20%, avoiding unnecessary surgery

Answer 96

Varying presentations/clinical course * Self limiting inflammation * Inflammation with risk of progression to fibrosis * Stable fibrosis * Progressive fibrosis with stabilisation posisble * Inexorably progressive fibrosis

Answer 97

Third leading cause of preventable death in the USA * *Increases risk of:** * *- heart disease** 23% * *- lung cancer** 17-30% - **COPD;** asthma exacerbations; **meningococcal meningitis** All **cause mortality increased by 15% in lifetime non-smokers** who live with smokers

Answer 98

**CSA** (due to instability of respiratory controller) * minimal hypoxia * minimal snore * gets better in REM **OSA** (due to anatomical obstruction) * hypoxia * loud snore * gets worse during REM \>80% of apnoeas have to be central to diagnose - i.e. no flow and no chest or abdo muscular effort

Answer 99

CURB65 • Confusion • Urea \>7mmol/L • Respiratory rate \>30 • BP \<90mmHg systolic or 60mmHg diastolic • Age \>65 Risk of death at 30 days (0-1 = outpatient; 2 = consider short stay in hospital or close observation as OP; 3-5 requires hospitalisation and consideration of ICU) * 0 – 0.6% * 1 – 2.7% * 2 – 6.8% * 3 – 14% * 4 – 27.8% * 5 – 27.8% SMART-COP is probably the better score to use as it identifies those which may deteriorate rather than those who are clinically obviously severe

Answer 100

**Severe - _F508del homozygotes_** * more often associated with pancreatic insufficiency * more often associated with OP * more often associated with DM **Less severe - F508del + other** **Least severe - other + other**

Answer 101

**90-95%** of asthmatics are sorted out by **ICS +- LABA** **Of that 5-10% separate into:** * refractory wit**h eosinophilia** or high IgE * in which case you go to the appropriate mab (**omalizumab IgE, mepolizumab** IL-5, with new ones coming) * refractory **non-eosinophilic** * in which case no good treatment but maybe dupilumab against IL-4r will be the go to in coming years

Answer 102

**Reduce inflammatory cells** and their activation * eosinophils, surface mast cells, activated T lymphocytes * switch off transcription of multiple genes that encode inflammatory proteins Of benefit in any age and severity * **prevent symptoms and exacerbations** * **reduce AHR** * **minimise irreversible changes** * **don't cure, only suppress** **ADR: Hoarseness and oral candidiasis** most common * no convincing evidence of impaired growth in children or OP in adults

Answer 103

**Muscarinic receptor antagonists** * **Prevent cholinergic induced bronchoconstriction** and mucous secretion * less effective than beta agonists as they **only affect the cholinergic reflex aspect** **Slower than SABA**s so should be **used only after** **Well tolerated** * most commonly dry mouth * the elderly more likley to get urinary retention or glaucoma

Answer 104

* **More indolent,** never presents with acute respiratory failure and hypoxaemia * **90% have peripheral eosinophilia** * Classic '**photographic negative pulmonary oedema**' * \>50% relapse after treatment with corticosteroids

Answer 105

Variable presentation, strongest predictor is exposure to an **antigen known to cause HP** **Acute** * 4-8hrs following exposure with intense fevers, chills, malaise, dyspnoea * resolves within hours/days without further exposure * note that usually no wheezing **Subacute** * Gradual onset over weeks * May occur as culmination of intermittent episodes of acute HP * Resolves over weeks/months without further exposure **Chronic** * Insidious onset makes diagnosis a challenge * Progressive dyspnoea, cough, fatigue, weight loss, clubbing * Can have irreversible component * May mirror IPF * Fibrotic phenotypes may be associated with bird antigens * Emphysematous phenotypes may be seen in farmer's lung (actinomycetes; fungus) **Chronic HP with parenchymal changes is associated with poorer prognosis** * Chronic pigeon breeder's lung has similar mortality to IPF **Diagnosis** * Careful occupation and home exposure history * May have ill defined micronodular or ground glass opacities on CXR * HRCT may be normal in acute; subacute characterised by groundglassing and centrilobular nodules; chronic may show reticular changes and traction bronchiectasis * May have subpleural honeycombing similar to IPF; but **spares the bases unlike IPF** * PFTs can be restrictive or obstructive * Useful for categorising physiologic impairment and gauging response to therapy * DLCO may be significantly impaired, especially in chronic HP with fibrotic changes * Serum precipitins * Assays for precipitating IgG antibodies against specific antigens * Often provide false negatives * Bronchoscopy * For BAL, which may show lymphocytosis which is characteristic but not specific to HP * note that there's no eosinophilia * Biopsy * Not necessary * Loose and **poorly defined non-caseating granulomas** * Differ from sarcoid where the granulomas are well defined * Mixed cellular infiltrate with lymphocytic predominance in alveolar spaces/interstitium

Answer 106

* Localised **dilation of vasculature associated** with ventilated alveoli. * Useful in **pulmonary hypertension or in severe ARDS**, where **optimisation of V/Q mismatch** can be helpful to improve oxygenation and ventilation. * Can **worsen oxygenation/ventilation in COPD due to significant number of partially ventilated alveoli to which flow is directed**

Answer 107

**\>90% of those with sarcoidosis** CTchest more sensitive but CXR preferred for characterising and following up * - peribronchial thickening, reticular nodular changes, predominantly subpleural **Stage 0 = normal Stage 1 = hilar adenopathy alone Stage 2 = hilar adenopathy plus infiltrates Stage 3 = infiltrates alone Stage 4 = fibrosis** **PFTs** * DLCO the most sensitive test for ILD * Restrictive defect can be seen but 1/3 with abnormal CXR and dyspnoea have normal volumes * ~50% have obstructive defect **PAH in \>=5%** * Found in 70% of those with end stage awaiting transplant * Sarcoidosis related PAH can respond to therapy

Answer 108

Normal sleep in adults is consistently organised from night to night * Progress through stages of non-REM Have bouts of **REM in cycles of 90-110 minutes** * 4-6 episodes per night * get progressively longer * associated with dreaming if awoken Slow wave = used to be called stage 3/4 * Slow wave sleep may be completely absent in older adults **Sleep duration** associated with **weight gain and mortality** * \<6hrs associated with more weight gain at 4yrs compared to more sleep * \<6hrs associated with increased mortality, seems to be mediated by inflammation

Answer 109

* *Oral steroids for \>=12 weeks** - induce **remission** - long term **doesn't prevent relapse** - slight increase in risk of invasive aspergillus * *Itraconazole** - **improves IgE**, radiology, QOL, symptoms - reduces prednisolone use - use for **4 months in those who're steroid dependent** * *Omalizumab** - overall **limited evidence** - decreases exacerbations and steroid use; reduces IgE and FeNO IgE level a marker of disease severity and treatment response

Answer 110

**Manage underlying disease if modifiable** * nontuberculous mycobacteria * IgG deficiency of whatever cause * ABPA * COPD **Acute exacerbations** * decisions made based on symptom changes rather than investigations * increased sputum, more viscous, darker, dyspnoea, haemoptysis * sputum MCS prior to abx to guide therapy * consider **eradication of pseudomonas when first isolated** (80% successful initially; free at median 14months f/u in 50%) **Prevention** * **Positive expiratory pressure therapy (chest physio):** improves **QOL/FEV1/FVC;** reduces sputum/inflammatory markers * **azithromycin reduces rates of exacerbation (**use in frequent exacerbators \>=3/yr or 2 hosp in 12 months) * need to **ensure no MAC colonisation first** * i**mmunisations** * inhaled aminoglycacides not clear in non-CF bronchiectasis * nebulised saline improves sputum bacteriology and QOL * nebulised dornase increases exacerbation frequency, hospitalisation, steroid/antibiotic use * inhaled steroids only with concommitant asthma/wheeze

Answer 111

Severe complications without severe obstruction unlikley solely due to COPD

Answer 112

Radiographic evidence of alveolar fluid accumulation without haemodynamic evidence of cardiogenic aetiology (PAWP \<= 18mmHg)

Answer 113

Most airlines recommend 6 weeks, though it has been shown to be safe to fly 2 weeks after radiological resolution of pneumothorax.

Answer 114

**Clinically** * COPD has less variability in symptoms * COPD never completely remits * COPD has less reversibility with bronchodilators * ~10% of COPD have features of asthma: eosinophils and response to OCS **PFTs (\>20% improvement psot bronchodilators quite specific for asthma over COPD)** * Asthma often fully reversible with bronchodilators * COPD may have increased TLC and decreased RV, indicated gas trapping and hyperinflation

Answer 115

Improves symptoms but very few are cured of mod-sev OSA with weight loss * degree of weight loss doesn't predict * significant improvement in sleep symptoms with weight loss * weight loss better than CPAP for metabolic benefits (CRP, insulin resistance, TGs) * both weight loss and CPAP improve hypertension in those with OSA Mod-sev OSA patients treated with CPAP tend to gain weight * thought due to feeling better -\> more of an appetite **Note that weight loss is an important adjunctive treatment when initiating CPAP for the metabolic benefits**

Answer 116

**Bronchodilators and corticosteroids the mainstay** **Bronchodilators** * SABAs: No evidence nebuliser more efficacious than MDI and spacer in asthma. Not extended to COPD but makes sense. * Neb = 10-12 puffs ventolin * Evidence for adding ipratropium mixed **Systemic corticosteroids** * Improve symptoms, FEV1, PaO2 in mod-sev exac * Reduced treatment failure, relapse, length of stay * SEs: insomnia, anxiety, depression, BSLs * 30-50mg/day * No advantage to IV. May be useful in first 24hrs in those in extremis and unable to take orals * **No benefit beyond 2 weeks** * **5 days likely adequate (no tapering needed)** **Antibiotics** * Controversy * Most benefit in those with all 3 symptoms: SOB, volume, purulence * More and more evidence that sputum purulence and ?CRP are the most important * ?CRP \>40 indication for antibiotics * In severe exacerbations decreases mortality and length of stay * Most only require oral antibiotics * Not unreasonable to start intravenous in the most severe exacerbations **Oxygen** * Use low concentrations aiming 88-92% SaO2. Use Prongs at 0.5-2L/min * ideally all patients with significant exacerbation need ABGs * Risk of worsening hypercapnoea: Alter V/Q matching, haldane effet, decrease hypoxic drive * High flow oxygen associated with increased HDU admission, NIV and LOS **NIV** * Indicated in hypercapnoeic respiratory failure * Use early in RR \>30 and pH \<7.35 * Improves biochemical markers * Decreases failure, length of stay, rates of intubation * Needs experienced nurses +/- HDU * Start at low pressures * **Aim to fix RR and pH within an hour** **Intubation** * Mortality 10-50%. Varying with QOL, age, acuity, comorbidities, length of ventilation, previous episodes * Weaning may be facilitated by NIV

Answer 117

**Thoracotomy the gold standard** * associated with considerable morbidity and mortality as patients usually unwell and with comorbidities **Drain size** * small bore drains effective * bigger drains = more pain and lower patient satisfaction **DNAse/tPA** * MIST-2 showed that **DNase + tPA intrapleurally decreases** need for surgical intervention (study endpoint was radiological and not mortality) * note that the study did this after standard drainage deemed ineffective * DNase alone -\> higher treatment failure

Answer 118

* *Dissolved** - 10% of CO2 in alveoli from blood from dissolved form **Bicarbonate** * *Carbamino compounds** - CO2 combined with terminal amine groups of blood proteins - Most importan globin of Hb, giving carbaminohaemoglobin

Answer 119

Those with pulmonary cause have oxygen benefit Exercise training improves 6MWT more than any other management option * *Pulmonary vasodilators** - Good for **group 1 (pulmonary artery hypertension)** - Maybe in 3,4,5 - **_NEVER in group 2 (cardiac cause)_**

Answer 120

MI within 3 months - 20% will die of reinfarction - within 6 months relative contraindication Uncontrolled arrhythmia FEV1 \<1L Hypercapnoea Severe pulmonary htn DLCO \<40% FEV1 \>2L can tolerate pneumonectomy FEV1 \>1.5L can tolerate lobectomy

Answer 121

No, harmful **_(note that CPAP also doesn't alter outcomes but is not harmful)_** **SERVE-HF trial in September 2015 NEJM** * LVEF \<=45% + AHI \>=15/hr and predominance of central events * Treatment: ASV + usual care vs usual care alone * Primary outcome - death from any cause, lifesaving cardiovascular intervention, unplanned hospitalisation for worsening HF AHI -\> 6.6/hr in ASV group All cause mortality (1.28; 1.06-1.55) and **Cardiovascular mortality** (1.34; 1.09-1.65) significantly **higher in ASV group**

Answer 122

No, but severity of outcome may be amplified Exceptions in presence of hepatitis C - Aspirin - Methotrexate - Isoniazid - HAART for HIV

Answer 123

Yes, very much so HRCT is a good, sensitive test. Not overly specific. * can give clues as to the cause of the infiltrate, e.g. fungal

Answer 124

NOO - is harmful! Landmark study in IPF

Answer 125

E.g. - muscular dystrophy - MND - Kyphoscoliosis - Diaphragm paralysis MIPS (maximal inspiratory pressure) on PFTs can be a good predictor of noctural hypoventilation - MIPS \<15-20 strongly predicts Of benefit - decreases mortality, hospitalisations, infections, symptoms

Answer 126

**Smoking = Intervention with the greatest mortality/FEV1 impact** Flu - Reduction in number/severity of exacerbations **Pneumococcal -** Reduces invasive disease * *Antibiotics** - Azithromycin has not become standard of care - Signficantly **increases time to first exacerbation** - Increased macrolide resistance - *No change in hospitalisations* **Simvastatin doesn't reduce exacerbation frequency** (NEJM 2014)

Answer 127

**No for mild intermittent** * Boushey et al NEJM 2005 * RCT of 225 pts * 200 budesonide BD vs placebo vs 20 BD zafirlukast * Exacerbation rescue: 800 budesonide BD for 10 days or 0.5mg/kg pred for 5 days * No difference between groups * exacerbation rate, QOL, rate of FEV1 decline over a year **Yes for persistent** * Pauwels et al Lancet 2003 * RCT of 7241 pts * - 400 daily \>11yrs, 200 daily \<11yrs budesonide vs placebo * 44% reduction in risk of hospital or ED treatment of asthma * Improved FEV1 from baseline prebronch 1.71% and postbronch 0.88% at 3yrs * Fewer courses of oral steroids and more symptom free days **Addition of LABA for mod persistent already on ICS** O'Byrne et al Am J Respir Crit Care Med 2001 From POV of exacerbations per year - bud 200 = bud 400 - bud 200 + eform ~30% reduction in exacerbations (vs 200 bud) - bud 400 + eform ~60% reduction in exacerbations (vs 400 bud)

Answer 128

Asthma COPD Bronchiectasis Bronchiolitis obliterans Alpha1 antitrypsin disease Cystic fibrosis

Answer 129

ARDS Neurogenic Altitude Re-expansion Opioid PE Eclampsia TRALI

Answer 130

Lung adenocarcinoma that is not yet apparent - need to keep a close eye on them - shouldn't be dismissed as infection

Answer 131

**All** * - Pulmonary rehab improves 6MWT, QOL, WHO class, VO2max but not haemodynamics * - Exercise training improves aerobic capacity and endurance * - Diuretics have no RCT evidence but are used * - Oxygen if hypoxic has no evidence but is used * - anticoagulation for (retro observational data): IPAH, drug induced PAH, hereditary PAH, CTEPH (not in CTD group) **Primary = at underlying disease** * - group 1: CTD and HIV if the cause * - group 2: OMT of heart failure * - group 3: underlying disease. Continuous oxygen (\>16hrs/day) if baseline PaO2\<55 confers survival benefit * - group 4: anticoagulation for 3 months, if no improvement then surgical thrombendarterectomy which may result in dramatic and sustained response (both lacking good data) * - group 5: variable at specific aetiologies **Advanced = pulmonary vasodilators** * - in WHO functional class II-IV despite treatment of underlying cause * - definite in group 1, almost never in group 2, case-by-case in 3-5 * - group 1: Improved survival, 6MWT, functional class, delayed disease progression, improved pulmonary haemodynamics * - group 2: increase mortality * - group 3: thought to worsen due to worsened V/Q mismatch * - group 4: could consider after thrombendarterectomy or if they're not fit for it or to bridge to surgery * - group 5: unknown role **Agents** * *- CCBs if vasoreactive on RHC** - improved survival, function, haemodynamics **Prostacyclin pathway** * - epoprostenol IV: first line in class IV (only medication with prospective evidence of improved survival) * - improves function, haemodynamics and survival in IPAH, unclear if in other group 1 * - iloprost inh: improves functional class and 6MWT but needs 6-9x/day * - selexipag: improves progression free survival and decreases hospitalisations, no change in mortality * Endothelin receptor antagonists * - nonselectives: bosentan, macitentan * - bos delays clinical worsening, improves haemodynamics and exercise capacity with mortality favourable to historical controls * - maci delayed clinical worsening, improves functional class and exercise capacity, improves combined morbidity/mortality endpoint * - selective against A: ambrisentan * - improves exercise tolerance, functional class, haemodynamics and QOL **NO-cGMP enhancers** * **PDE5 inhibitors: sildenafil, tadalafil** * sild: improves haemodynamics and exercise capacity * tada: improves time to clinical worsening and exercise capacity **Riociguat** * Stimulates soluble **guanylate cyclase** * increases sensitivity of sGC to endogenous NO; direct stimulation of NO receptor * improves 6MWT, WHO class, symptoms, PVR * unknown if mortality benefit **End stage** * - lung transplant and creation of R-\>L shunt

Answer 132

**During RHC** * - short duration vasodilator administered * - decrease in PAMP \>=10mmHg to an absolute level of \<=40mmHg without decrease in CO or BP In these patients long term treatment with a dihydropyridine or diltiazem CCB confer survival, functional, and haemodynamic benefit - use outside of vasoreactivity worsens outcomes

Answer 133

**DIP** * - Smoking related form of ILD (one of the rarest forms) * - Diffuse groundglass opacities, usually basal and peripheral * - pigment laden macrophages fill alveoli on histology * - good prognosis with smoking cessation and steroids **RBILD** * - related to DIP, some feel that DIP is just end stage RBILD

Answer 134

Cardio/pulmonary/vascular risk - doubles CV risk Sleepiness and QOL Noise pollution Post-operative risk

Answer 135

**Loss of elastic tissue** * - enlarged alveolar ducts -\> loss of surface area for gas exchange * - decreased lung recoil -\> maximal exercise limit to expiratory flow and produces dynamic lung hyperinflation Increased stiffness of the chest wall Flattened and less efficient diaphragm **Physiology** * - DLCO decreases 5%/decade * - increased V/Q mismatching * - increase in A-a gradient * - decreased response to hypoxaemia and hypercapnoea * - decreased mucociliary clearance

Answer 136

Aims of asthma therapy * minimal chronic symptoms, ncluding nocturnal * minmal exacerbations * no emergency visits * minimal use of SABA * no limitations on activities, inclduign exercise * Peak exp flow circadian variation \<20% * normal peak flow exp flow * minmal ADR from medicine **Education improves compliance, especially with ICS** * also helps to recognise worsening asthma and how to step up * Written action plans reduce admissions and morbidity in adults and children

Answer 137

Some studies show higher patient preference and adherence * - no benefit regarding apnoea/hypopnoea and oxygen desaturations CPAP equally effective compared with BiPAP in OHS * - both improve daytime hypercapnoea in those without severe nocturnal hypoxaemia

Answer 138

**Bronchial obstruction** * - tumours * - hilar lymphadenopathy * - COPD * - mucoid impaction (ABPA) **Immunodeficiency** * - IgG: bruton's, CVID, subclass deficiency * - IgA: selective, ataxia telangiectasia * - CGD **Abnormal clearance** * - ciliary defects: ciliary dyskinesia * - cystic fibrosis * - Young's: obstructive azoospermia with sinopulmonary infections **Miscellaneous** * - A1AT * - infections: childhood, bacterial, viral, other * - recurrent aspiration pneumonia * - CTD: RA/Sjogren's * - IBD * - chronic rejection post transplantation

Answer 139

Parenchymal - IPF - Drugs - Amiodarone, bleomycin, methotrexate, nitrofuraontoin - CTD - SLE, systemic sclerosis, RA, sarcoid, vasculitidis - Environmental - Asbestosis, silicosis, hypersensitivity pneumonitis - Radiation Neuromuscular Weakness - GBS, ALS, muscular dystrophy, myasthenia gravis Chest wall/pleural - Kyphoscoliosis - Ankylosing spondylitis - Effusion - Morbid obesity

Answer 140

Tracheal stenosis and goitre

Answer 141

Idiopathic - pachydermoperiostosis, familial clubbing, hypertrophic osteoarthropathy Pulmonary - lung cancer, pulmonary metastases, pleural mesothelioma - ILDs, sarcoidosis, cryptogenic fibrosing alveolitis - lung hydatids Cardiac - cyanotic congenital heart disease - any right to left shunt - IE Gastrointestinal - IBD - PBC, cirrhosis, hepatopulmonary syndrome - achalasia, peptic ulceration of the oesophagus Skin - Bureau-Barrière-Thomas syndrome, Fischer syndrome, palmoplantar keratoderma, and Volavsek syndrome Malignancies - Thyroid - Hodgkins, disseminated CML, POEMS Miscellaneous - acromegaly, thyroid acropachy, severe secondary hyperparathyroidism - sickle cell - pregnancy

Answer 142

Increased: - residual volume and FRC - V/Q mismatching - airway reactivity - compliance Decreased - FEV1 - FVC - DLCO - respiratory drive in response to hypoxia and hypercapnoea Unchanged - TLC

Answer 143

* *Asbestosis** - Irregular linear opacities in lower lung fields - Groundglassing - Curvilinear lines parallel to the pleural surface - Pleural thickening * *Silicosis** - Crazy paving pattern - Calcified hilar nodes - Small, rounded upper lobe opacities - May coalesce as disease progresses and form large, non-segmental conglomerates of irregular masses - Simple = small, rounded opacities without PFT change - Complicated = coalescing - Progressive massive fibrosis = large masses * *Coal worker's pneumoconiosis** - Identified in 10% of all coal miners - Nodules similar to silicosis - May cause chronic bronchitis and COPD - May progress to PMF as in silicosis

Answer 144

* *Cough with daily production of mucopurulent and tenacious sputum for months/years the classics** - dyspnoea, wheeze, pleuritic chest pain less so - urinary incontinence common * *Look for some underlying cause** - infective, obstructive, immunodeficiency, etc * *Imaging** - CT preferred - airway **dilatation** (\>1.5x diameter of adjacent vessel) * *- signet ring** sign classic * *Distribution** * *- perihilar: ABPA** - **upper: cystic fibrosis** - ML/LL: primary ciliary dysfunction - ML/lingular of LUL: nontuberculous mycobacteria - LL: idiopathic

Answer 145

* **Shunt:** Perfusion to non-ventilated alveoli * **Deadspace:** Ventilation to non-perfused areas

Answer 146

Hb is purple, so decrease in bound O2 results in purple colour

Answer 147

2,3 DPG best binds to the **beta subunit**, so HbF has less 2,3 DPG. * Results in an oxygen dissociation curve shifted to the **left (HbF has higher affinity for oxygen)** \*\* DPG - promotes hemoglobin transition from a high --\> **LOW-oxygen-affinity state (shifts curve to the right)**

Answer 148

FEV1/FVC \<70% predicted Severity is categorised based on FEV1 - Mild \>70% - Mod 50-69% - Severe \<50% Reversible - Increase in FEV1 by \>=12% and \>=200mL after bronchodilators - Asthma typically fully reversible, COPD not.

Answer 149

SABA for 4hrs LABA for 12hrs Tiotropium for \>24hrs

Answer 150

Either dir**ect stimulation of bronchoconstriction**, or **activity** to induce release of histamine. Performed to ru**le out exercise or allergen induced asthma** when standard **PFTs normal** 1. Inhaled **metacholine (direct challenge**: cause **direct constriction** via receptors on smooth muscle) * Highly **sensitive** but not specific * \>=20% reduction in FEV1 with 4mg/mL metacholine is positive 2. Inhaled **mannitol** (indirect challenge: **cause activation of mas**t cells -\> histamine + **bronchoconstrictor** release) * Highly specific but but not sensitive * \>=15% reduction in FEV1 with \<=635mg inhaled mannitol 3. Exercise challenge * Excellent spec and sens for exercise induced bronchoconstriction * Baseline spirometry followed by 80-90% maximum HR treadmill held for 8mins * \>=10% decline in FEV1 or FVC over any two consecutive timepoints at 1, 3, 5, 10, 15, 20, 30, 45 mins

Answer 151

NORMAL expiration flow **LIMITED inspiratory** flow

Answer 152

LIMITED expiratory flow (as the obstruction moves IN with expiratory as it INTRAthoracic pushs IN on it) PRESERVED inspiratory flow (as the obstruction moves out with inspiration as it is INTRAthoracic)

Answer 153

Indicative of **fluctuating upper airway obstruction** * Neuromuscular weakness * Parkinson's disease * OSA * Upper airway burns * Pedunculated tumours * Laryngeal dyskinesia

Answer 154

**TLC defines a restrictive defect. FVCTLC is required in the definition** **RV (residual volume):TLC (Total lung capacity)** tells you the ratio of unusable lung * **Increased** RV:TLC points toward **extrinsic restrictive** defect * **normal** RV:TLC points toward intrinsic restrictive defect

Answer 155

Amount of **CO that can bind to Hb** **Decrease** * Diffusion problem * Thickened membrane * Fibrosis, alveolitis, vasculitis * Decreased surface area * COPD * Decreased capillary blood volume * Anaemia * PE * HF * Decreased lung volume (previous lobectomy) **Increase** * Polycythemia * Asthma * Increased blood volume * Left-\>right shunt * Alveolar haemorrhage * Suspect if DLCO intially high then decreased subsequently

Answer 156

KCO shows **gas exchange per unit volume of lung,** accounting for change in lung volume **Low** in **pulmonary** causes of decreased DLCO * ILD, fibrosis, pulmonary vascular disease **High** in **extrapulmonary** causes of decreased DLCO * Resection, thoracic wall abnormalities

Answer 157

Autosomal recessive exocrinopathy due to mutations on **chromosome 7** **F508del most common** * 70% defective alleles * 90% individuals carry \>=1 F508del mutation **Ivacaftor o**f benefit in individuals with G**551D stop mutation (~4% of CF)** * ~8% have this mutation * improves **FEV1 7-10%**, reduces e**xacerbation by 55%**, reduces hospitalisation, gains BMI **Lumacaftor-ivacaftor** of minor benefit in **individuals homozygous for F508del** * lumacaftor partially corrects misfolding * *ivacaftor improves channel gating activity* * 3% increase in FEV1, reduced exacerbation freq by 39%, small improvements in BMI and QOL * similar benefit to that of inhaled tobramycin

Answer 158

**Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)** * epithelial ion channel * apical plasma membrane of acinar and epithelial cells **Inability to transport chloride ions**, affecting different tissues in different ways * Overriding principle is that of **thickened secretions due to lack of periciliary layer caused by decrease in water**

Answer 159

**6** * Class I * Absence of synthesis * Class II * Defective protein maturation and premature degradation * F508del accounts for ~70% of defective alleles * 90% individuals carry \>=1 F508del mutation * Class III * Disordered gating/regulation * Class IV * Defective conductance through the ion channel pore * Class V * Reduced number of CFTR transcripts due to promoter/splicing abnormality * Class VI * Accelerated turnover from cell surface

Answer 160

Caucasians * 1/25 carry * 1/3,300 live births in caucasians * 1/33,000 live birth in asians

Answer 161

Thick sputum is difficult to clear which leads to c**hronic infection and inflammation.** This then leads to **bronchiectasis,** typically in the **upper lobes.** **Chest physiotherapy** * daily required **Mucolytics** * DNase and hypertonic saline of benefit * inhaled steroids and bronchodilators only of benefit in those with asthma phenotype

Answer 162

**Pancreatic** * exocrine insufficiency * **80-90% of those with CF** * due to bl**ockage of ducts** due to thickened and inspissated mucous * **fat soluble vitamin** replacement * **pancreatic enzyme** replacement * requires **PPI** as they don't function in acidic environment * endocrine insufficiency * \>30% of adults with CF * features o**f type 1 and 2** * yearly oral GTT recommended to screen (fasting BGL and HbA1c low sens) * **treated with insulin**, never with diabetic diet * decreased nutrition decreases BMI which worsens PFTs **Liver** * CF related liver disease usually develops before 18yrs of age * ~10% CF patients develop cirrhosis * **hepatic steatosis most common at ~60%** * multilobar or focal biliary cirrhosis may be associated with portal hypertension and splenomegaly * no benefit to ursodeoxycholic acid * may progress to failure requiring transplantation **GORD** * requires aggressive treatment with PPI to reduce microaspirations **Gallbladder** * microgallbladder in 25-30% * cholestasis and cystitis **Intestinal** * **meconium ileus** in 10-20% newborns with CF * distal intestinal obstructive syndrome in adults * c. difficile infection presents atypically, not usually with diarrhoea but with pain **Genitourinary** * involution of vas deferens in 99% males * functioning spermatogenesis * amenorrhoea and anovulation in females **Renal** * diabetic nephropathy * oxalate nephrolithiasis **Haematological** * anaemia of chronic disease * functional iron deficiency * hypersplenism * high INR **Musculoskeletal** * clubbing * seronegative arthropathy * pANCA positivity

Answer 163

**Major predictors** * FEV1. Expected decline 2%/yr * WCC * Low BMI * High CO2 * Female gender **Decline** * new bacteria * especially pseudomonas, MRSA, MAC, burkholderia cepacia, stenotrophomonas * diabetes * ABPA * poor social situation or poor compliance * poor nutrition * *Lung transplant indicated when 5yr survival \<30%, best proxied by FEV1 \<30%** - 60% survival at 5yrs after transplant May also be indicated with **precipitous decline,** especially when **female or diabetic;** massive **haemoptysis or malnutrition;** or **pulmonary hypertension** in the absence of hypoxaemic exacerbation

Answer 164

**Staph aureus most common** * MRSA becoming increasingly common, up to 25% prevalence * MRSA independent risk factor for death **~70% of adults chronically infected with p. aeruginosa** * prolonged infection results in conversion to mucoid phenotype due to production of alginate * chronic infection an independent risk factor for **Dual anti-pseudomonal cover** * antipseudomonal beta lactam + one of fluoroquinolone, aminoglycacide (tobramycin preferable), or colistin * utilise past sensitivities **Azithromycin and inhaled anti-pseudomonals** (aztreonam, tobramycin) have been demonstrated to improve number of exacerbations an**d FEV1 when administered chronically in those colonised with pseudomonas** **Burkholderia cepacia complex** is associated with **accelerated decline in PFT and decreased survival** * treated with bactrim * contraindication to transplant in some centres **Isolation of MAC** should result in i**mmediate cessation of azithromycin prophylactic therapy to preserve sensitivity**

Answer 165

**Lung Ca** 8% men, 6% women * - note that incidence in men has fallen dramatically whereas woman is plateauing/slightly going up * *10x risk smokers** compared to never smokers * *20x risk in continuin**g smokers * stopping in middle age ameliorates **90% of the additional risk**

Answer 166

**Small Cell** * Neuroendocrine markers * CD56, neural cell adhesion molecule, synaptophysin, chromogranin * ~100% association with smoking **Non-Small Cell** * 90% of epithelial lung cancers * **Adenocarcinoma** * Most common subtype * Glandular differentiation or mucin production * Thyroid transcription factor-1 positve in 70% * Napsin-A positive in \>90% * **Squamous** * Morpholigcally identical to those outside the lung * Sheets of cells with keratinisation or intercellular bridges arising from bronchial epithelium * more likely to be cavitating than the others * **Large cell** * \<10% of all lung cancers

Answer 167

**Small cell and squamous** * ~100% of SCLC is associated with smoking All lung cancer subtypes can occur in smokers

Answer 168

**Not currently recommended in Australia** **High risk patients** * Current smokers 55-80yrs old with \>30pck/yr smoking Hx * Ex smokers of \<15yrs and 55-80yrs old As per the **National Lung Screening Trial** in **NEJM 2011** * 53,454 pts 55-74yrs with \>30pck/yr smoking and no symptoms * 3x annual LDCT vs 3x annual CXR, primary endpoint all cause mortality * **Annual screening decreased mortality by 20%, despite 96% false positive rate** * 27% of initial LDCT had a nodule \>4mm

Answer 169

**Common, especially in SCLC but not exclusive** **PTH** * Mostly with squamous **ADH/ANP** * SIADH (classic for **SCLC)** * Usually resolves within a month of chemotherapy * Look for ANP if hyponatraemia doesn't resolve with fluid restriction **ACTH (think SCLC)** * Usually with electrolyte disturbances rather than Cushing's * Usually resolves with chemo * Can perform bilateral adrenalectomy if extreme **Skeletal/connective tissue** * Clubbing ~30%, **HPOA 1-10% (think SCC)** * Neurologic-myopathic syndromes (think SCLC) ~1% **CNS** * Anti-hu, anti-CRMP5, ANNA-3 Anorexia, cachexia, immunosuppression, fever, weight loss

Answer 170

**Both require imaging and tissue sampling** **NSCLC staged with TNM** * CTCAP first * If mets then no PET. If no mets then PET * **PET upstages 20%**, avoiding **unnecessary surgery** **SCLC staged with limited vs extensive disease** * CTCAP + MRIB +/- bone scan * hepatic/adrenal disease common * CNS involvement in 10% asymptomatic * MRI spine in those with cord compression signs/symptoms for consideration of palliative resection/radiotherapy **Limited disease confined to a ipsilateral thorax within a tolerable radiation port** * median survival **12-20months, 5yr ~10%** **Extensive disease overt metastatic disease by imaging or clinical exam** * median survival **7-11months,** **5yr ~1%** **Significant implication for survival and cure rates**

Answer 171

**Stage I-II NSCLC** require **resection** if patient amenable and appropriate for surgery IIIa NSCLC can be considered with mediastinal clearance in certain patients **_Surgical resection not_** recommended in **SCLC due to micrometastases even in early stage.** May be considered in clinical stage I when invasive mediastinal staging clear and with adjuvant chemotherapy **Contraindications to curative resection in NSCLC** * Extrathoracic metastases, metastases to supraclavicular node, contralateral lung/mediastinum * SVC syndrome * Malignant effusion * Tamponade * Tumour within 2cm of carina * Involvment of main pulmonary artery

Answer 172

Worsens outcomes in Ia Possibly improves in Ib **Definitely improves in II-IIIa** * - LACE study 5.4% improved survival at 5yrs with chemo + surgery compared to solo surgery * No evidence of benefit to \>4 cycles * *Platinum based** but no particular regimen optimal * *- Cisplatin or carboplatin** +/- other depending on subtype - EGFR erlotinib or gefitinib - ALK crizotinib - If neither then bevacizumab (shouldn't be used in squamous or CNS involement due to bleeding risk)

Answer 173

**~40% present with metastatic disease** Mean survival **4-6months** **Symptom** control very important * *Chemotherapy** improves s**ymptoms, quality of life, and survival - appropriate in ECOG \<=2 with few comorbidities** **Look for specific mutation** * **EGFR** * gefitinib/erlotinib * Doesn't work if RAS present * **ALK crizotinib** * mutually exclusive with EGFR **Platinum based first line** * cisplatin/carboplatin + either vinorelbine, paclitaxel/docetaxel, gemcitabine * response rate ~30% * increases meadian survival from 6 to 9 months **Addition of anti-VEGF (bevacizumab) improves survival** * HTN (predicts response), haemorrhage (especially in squamous or CNS), impaired healing, GI, skin, leukopoenias Non-squamous has better outcomes with cisplatin + pemetrexed Squamous has better outcomes with cisplatin + gemcitabine

Answer 174

**Surgical resection not recommended even in stage I disease due to prevalence of micrometastases** **Chemotherapy** * **platinum** based * cisplatin/carboplatin + etoposide, ironotecan * or cyclophosphamide, doxorubicin, vincristine if not tolerated * Response rates ~80% but survival still abysmal (LD median 12-20months, 5yr 6-12%)(ED median 7-11months, 5yr ~1%) **Radiotherapy (60Gy in 30#)** * Standard part of induction in LD with good performance status * **Improves survival** by 5% compared to sole chemo * Better toxic profile with cisplatin + etoposide * **Prophylactic cranial given in complete response due to 100% 2yr CNS disease** **Extended stage** = **_palliative_** RTx and chemotherapy

Answer 175

Dizziness, dry mouth, parasthesias in hands/feet, chest pain Rapid, shallow, irregular breathing with frequent sigh breaths

Answer 176

Late in the disease process. Very rare to present with respiratory weakness as the first symptom

Answer 177

**10-12% adults** Usually **each patient sticks within their own severity** **Risk factors for death:** * Poorly controlled * Poor compliance with ICS * Previous near fatal asthma * ICU admission or intubations

Answer 178

**Risk factors** * Atopy the major one * Those without unlikely to develop asthma * Genetics * Polygenic * ADAM-33, DPP-10, ORMDL3, Arg-Gly-16 for decreased beta ag response, 5-lipooxygenase repeats for decrease leukotreine antagonist response * Hygeine hypothesis * Lack of exposure to infections pushes toward TH2 cell bias which is allergenic response * Exposure associated with TH1 cell bias * Obesity * Independent risk factor for development * Occupational * Common, 10% young adults * Suspect when symptoms abate on weekends and holidays * Removal from exposure within 6 months usually results in complete resolution without airway damage * Intrinsic * ~10% * Normal IgE and negative skin prick * Usually more severe and persistent with later onset **Triggers** * Pollutants * Allergens * Activate mast cells with bound IgE * Exercise * Physical * Cold air, hyperventilation, laughter, perfumes * Infections * Rhinovirus, coronavirus, RSV most common triggers of acute exacerbations * Occupational exposure * Drugs * beta blockers, aspirin **Don't make a difference** * diet * GORD * ACEI

Answer 179

**Epithelial shedding** * Loss of barrier function and exposure of sensory neurons * Loss of enzymes for degrading inflammatory mediators * Loss of relaxant factors **Thickening of basement membrane** * subepithelial type III and V collagen deposition * feature of eosinophilia * In severe the airway itself may be thickened, leading to irreversible narrowing **Oedematous and thickened airway wall** * especially in fatal **Mucous hypersecretion and plugging** * glycoproteins from increased number of goblet cells and plasma protein exudate * Hyperplasia of submucosal glands in large airways **Vasodilation and angiogenesis** * VEGF involved **Airway smooth muscle hypertrophy/hyperplasia** * PDGF, endothelin 1 * Reduced response to beta agonism, likely resulting from uncoupling of receptors or chronic inflammation altering resting membrane potential **Altered neural regulation** * Secondary effect * Reflexive cholinergic activation * Inflammatory activation of sensory neurons * Reflex cholinergic bronchoconstriction, release of inflammatory neuropeptidases * Hyperalgesia * Neurotrophin release, sensitising and proliferating * Release of substance P

Answer 180

NO is derived from ai**rway epithelium and promotes dilation of blood vessels and airways** * vasodilation -\> promotes oedema -\> worsen obstruction Measurement can be useful to **determine compliance with ICS** * high NO implies active inflammation, which points toward non-compliant or not working No convincing evidence that using NO to titrate ICS improves outcomes

Answer 181

**_Biologicals for severe asthma_** **Asthma type** **Target** **Molecule** Allergic asthma IgE Omalizumab Eosinophiliac asthma Il-5 or Il-5 receptor Mepolizumab, benralizumab * These monoclonal Abs are used in **addition to ICS + LABA.** * In appropriately selected patients, mABs induce ~**50% reduction in exacerbations** * Oral steroid sparing * Modest improvements in lung function Add on therapies for severe asthma * **_Long term oral steroids should be avoided where possible_**

Answer 182

Beta 2 receptors coupled via G proteins to adenyl cyclase, increasing intracellular cAMP * relax SM, inhibit mast cells, reduce plasma exudate, reduce neural stimulation * inflammatory cells rapidly downregulate their receptors, so little effect on AHR **SABAs** * 3-6hr duration * Increased use indicates poor control **LABAs** * \>=12hr duration * Use without comcommitant ICS worsens outcome (doesn't treat underlying inflammation) * Improve **control and reduce exacerbations** when added to **_ICS_** Side effect m**ainly tremors, mainly in the elderly** Large reserve of beta 2 receptors in smooth muscle means even with downregulation they're still effective * less so with mast cells, where ICS helps counteract downregulation

Answer 183

* Non-selective PDE inhibitor relaxing smooth muscle * Used rarely as an adjunct when on maximal other medications * Arrhythmias associated with higher levels \>10mg/L - rarely observed below this * Most commonly nausea, vomiting, headaches * Largely inactivated by the liver

Answer 184

**During moderate-severe exacerbations** * oral equivalent to IV * 30-45mg daily for 5-10days, no taper required **~1% require maintenance** * should be titrated to the minimum dose required to suppress symptoms and avoided when possible! **Multiple side effects** * truncal obesity, bruising, OP, diabetes, HTN, gastric ulcers, proximal myopathy, depression, cataracts * monitoring of bone density allows for treatment with bisphosphonates

Answer 185

May be added in those not controlled on low dose ICS * less effective than LABA **Inhibit cyc-LT1 receptors**

Answer 186

Called **aspirin exacerbated respiratory disease (AERD)** **7% of asthma sufferers get worse with COX inhibitors** * 14% with severe asthma * need to ensure it's not to a single agent, as that may be IgE mediated allergy **Phenotype (clinical diagnosis the rule)** * perennial rhinitis * nasal polyps * non atopic * late onset 80% have upper or lower airway reactions to alcoholic drinks **NSAID reaction** * 30mins-3hrs after ingestion * dose related, can be as bad as fatal * urticaria/angioedema in 15% **Pathophysiology** * due to baseline dysregulation in arachidonic acid metabolism with balance shifted toward leukotrienes * primary cell producing it is bronchial mast cells * COX-1 inhibition exaggerates the dysregulation, thought to be by reducing PGE2 which is a 'brake' on leukotrienes Triggered by COX inhibitors but present even in their absence Safe to use COX2 inhibitors * some exquisitely sensitive people may be triggered by them Management * Asthma as per usual guidelines * COX-1 avoidance unless being desensitised * leukotriene antagonists vastly improve airway symptoms and exacerbation rate

Answer 187

**1/3 get better, 1/3 stay the s** with mod/sev asthma **Prednisone better** than prednisolone as foetal liver can't convert prednisone to prednisolone **Breastfeeding safe**

Answer 188

~20% More **severe disease**, more **frequent admission**, faster decline in PFTs, **higher risk of death** **Interferes with anti-inflammatory action** of corticosteroids, requiring higher doses **Cessation improves PFTs** and reduced steroid resistance

Answer 189

Exposure and sensitisation to an antigen leading to inflammation of the alveoli and small airways. Sensitisation is necessary but not sufficient for developing HP; many sensitised individuals don't develop HP. TH1 inflammatory pattern with emerging evidence of TH17 subsets involved Fungal, bacterial, mycobacterial, bird-derived, and chemical causes.

Answer 190

* **Antigen removal the mainstay** * **Corticosteroids may help** in decreasing duration of symptoms but don't change outcomes * - 0.5-1mg/kg for 1-2/52 followed by 2-6/52 taper * **Fibrotic changes associated with chronic HP may be irreversible**

Answer 191

* Males 20-40 with **no history of asthma** * Not associated with peripheral eosinophillia, not typically not until 7-30 days * **HRCT is always abnormal** or reticular opacities with small pleural effusions * characterised by **high pH with marked eosinophilia** * **bilateral groundglassing**

Answer 192

* *R-\>L intrapulmonary shunt** - CCF - ARDS - Pneumonia * *V/Q mismatch** - PE - Atelectasis - Pneumonia - Obstruction - Pneumothorax * *Alveolar hypoventolation** - ILD * *Hypoventilation** - Neuromuscular disorders - CNS disorders

Answer 193

* *Ferric (3+) iron in heme** - due to **oxidation of Fe2+ -\> Fe3+** - Unable to bind O2 - Affinity of the remaining ferrous heme groups is increased - Functional anaemia! * *Congenital** - May be asymptomatic - Cyanotic, slate blue skin and mucous membranes * *Acquired** - Drugs usually Acquired treated with **cessation of the cause** and **methylene blue or hydroxycobalamin.** Congenital best treated by avoiding medications that induce methaemoglobin

Answer 194

**Prothrombotic states** * Common * **Factor V leiden**: causes **resistance to activated protein C** * **Prothrombin gene mutation**: increases **plasma prothrombin concentration** * **Antiphospholipid syndrome** - **most common** acquired cause of thrombophilia * **Rare** * **Deficiency of: antithrombin, protein C, protein S**

Answer 195

d-dimer increased in those \>70yrs - not affected by smoking - false positives in: sepsis, AMI, cancer, pneumonia, post-operative state, 2nd/3rd trimesters of pregnancy

Answer 196

Describes a regional pattern of acute right ventricular dysfunction - **Hypokinesis of RV free wall** with normal or hyperkinetic RV apex. ## Footnote **Best known indirect sign of PE**

Answer 197

**60 x** baseline risk, **synergistic risk** Mesothelioma doesn't appear related to smoking. Even short term exposures of asbestos in the distant past can be associated with development of mesothelioma

Answer 198

**Silica** is toxic to **alveolar macrophages** Result in **higher risk of infections** requiirng these as primary defence - **TB, atypical mycobacteria, fungi - Treatment of latent TB is longer** May **develop connective tissue disorder** * *- RA or systemic** sclerosis - **Caplan syndrome** is the combination o**f seropositive RA** with **pneumoconiotic nodules** in the lung - First described in **coal workers**

Answer 199

May present with **acute pneumonitis** More commonly it presents with a **chronic granulomatous disease similar to sarcoidosis** * Differs by evidence of **specific cell mediated response to beryllium** * **Delayed hypersensitivity** reaction **Beryllium lymphocyte proliferation test** * Compares in vitro proliferation of lymphocytes from blood or BAL in the presence of beryllium salts to unstimulated cells * Usually measured by uptake of radiolabelled thymidine In beryllium sensitised individuals non-caseating granulomas or monocytic infiltration on lung biopsy establishes the diagnosis

Answer 200

Used to provide **butter flavour** to popcorn Has been associated with **bronchiolitis obliterans**

Answer 201

Progressive **chronic airflow limitation** which is **not fully reversible** **5th leading cause o**f death **worldwide,** almost equal burden between genders Prevalaence by spirometry * - 7.5% in \>40yrs * - 29% in \>75yr Prevalence by symptoms * - 30% describe wheeze, 25% SOBOE in past 12 months **COPDX** * **C**onfirm diagnosis * **O**ptimise function * **P**revent deterioration * **D**evelop support * **X** - manage exacerbations

Answer 202

**No universally** **accepted definition** Change in symptoms **out of keeping of their normal variation** * Dyspnoea * Purulence * Volume No objective diagnosis in 50% **Respiratory infection (50-70%)** * Bacterial: h influenzae, s pneumo, m catarrahalis, mycoplasma, chlamydia; pseudomonas, staph in more advanced * Viral: influenza, rhinovirus, RSV, metapneumovirus **Non-infectious:** * Pollution * PE: ~1 in 4 exacerbations without clear cause * CCF * Pneumothorax * Sedation * Anxiety **Hospitalisation** * Failed OP management * Unable to manage at home due to breathlessness: Mobilising, sleeping, eating * Severe comorbidities * Confusion * Worsening gas exchange * New arrhythmia

Answer 203

**Cigarettes** * - Accounts for \>95% burden of diease * - Only 10-20% develop clinical disease * - ~50% have some airflow limitation Organic/inorganic dusts (cadmium, coal, cotton, cement, grain) Smoke from cooking Bronchial hyperresponsivenes Genetics * - alpha 1 antitrypsin * - 1-2% of population Infections/mucous hypersecretion

Answer 204

Pharmacologic therapies useful in reducing symptoms, improving QOL, and reducing exacerbations but not improving survival or slowing decline of FEV1 **Mild (FEV1 \>60%)** * SABA only: terbutaline, salbutamol **Moderate (FEV1 \<60%)** * Anticholinergic (LAMA): ipratropium; tiotropium, glycopyrronium, aclidinum, umeclidium * LABA: salmeterol, eformeterol * VLABA: indacterol, olodaterol * Reduced dyspnoea, improved QOL, reduced exacerbations * Longer acting and newer medications probably better than salmeterol/eformeterol * Some concerns about CV effects of tiotropium, with risk/benefit usually falling on benefit side * Multiple combination medications: ICS + LABA, LAMA + LABA/VLABA Mod/sev (FEV1 \<50%) with frequent exacerbations * Addition of inhaled corticosteroids (ICS) reduces symptoms, *improves QOL, reduces exacerbations* * Combination with **LABA may slow decline in FEV1** * SEs: increased pneumonia, easy bruising, cataracts, ?OP * budesonide doesn't seem to increase pneumonia, fluticasone dose **Others** * Theophylline: Modest bronchodilator effect. New data indicating low dose may have anti-inflammatory and immunomodulatory effects * PDE4 inhibitors: Anti-inflammatory with moderate fficacy as add on to LABA. Not TGA approved * Mucolytics: May improve clearance and decrease exacerbations. High dose NAC shows promise Severe with respiratory failure * **Continuous oxygen therapy: _Improves mortality_** * PO2 \<55 or \<60 with pulm HTN or RHF * Only beneficial if used \>=16hrs a day * Portable oxygen not shown to have mortlaity benefit Beta blockers are safe in COPD * **_LVRS: Rarely in Australia_**. Predominant upper lobe emphysema benefit the most. * Overall early increased mortality with no change at 2yrs, with increased exercise capacity * Bronchoscopic techniques: *valves, plugs,* steam, airway bypass * Transplant: Young with severe disease casuing significant morbidity Additional * QOL: Questionnaires, self reported dyspnoea * Exercise tolerance * Bone density: Significant number of mod/sev COPD population have OP, and do worse

Answer 205

Generally don't die of COPD, even in severe disease. Top are **CVS and cancer**

Answer 206

* *pneumophila** = *cooling towers and humidifiers* * *longbeachae** = *potting mix* **Risk factors** * older, smokers * immunocompromised * chronic cardiac, resp, renal disease * Diarrhoea, neurologic findings,* and **temp \>39** * *Hyponatraemia,** elevated LFTs, haematuria **Distinctive rounded, nodular opacities** * Especially in the immunosuppressed **Management** * azithromycin, moxifloxacin

Answer 207

* *Underlying lung diseases* * *Bronchiectasis, pneumoconiosis, COPD, CF, alpha 1 antitrypsin deficiency, primary ciliary dyskinesia*

Answer 208

First 7 generations have cartilage rings

Answer 209

**Air flow variability** * diurnal and between day variability * gold standard for diagnosis of occupational asthma is day to day variability with bad days while at work (measured with peak flow) **Reversibility** * **pre and post bronchodilator** * **\>12% and 200mL** **Airway tests of airway hyperresponsiveness** * **direct** = **metacholine test, sensitive BUT NOT specific.** Good to look for perisistent airway remodelling * **indirect = mannitol, hypertonic saline.** good measure of the inflammatory component. **specific BUT NOT sensitive**

Answer 210

**Abnormal irreversible bronchial dilation** * - HRCT gold standard **\>=1 dilated bronchi** * - internal luminal diameter exceeding diameter of adjacent arteries Clinically characterised by small airway obstruction, Causes - see list, but think 'chronic infection and airway destruction'

Answer 211

Also known as **obliterative bronchiolitis** and **bronchiolitis obliterans** **Pathology** * peribronchiolar fibrosis * cicatrization of the bronchiolar lumen * *fibrosing inflammatory process surrounding the lumen* * *extrinsic compression* and obliteration of the airway **Causes (result of immunological injury)** * Allograft (lung, heart-lung, SCT) * Postinfectious * Connective tissue * Inhalational injury * Drugs **Clinical** * Severe, progressive small airway obstruction with dynamic hyperinflation * CXR is normal or nonspecific * On HRCT mosaic decreased attenutation. Evidence of gas trapping variability between neighbouring airways on expiration

Answer 212

* Upper airway reflexes * Cilia * nonspecific and specific. e.g. smoking vs cilia diskinesis syndrome * Mucous * nonspecific and specific. e.g. chronic bronchitis from smoking vs CF * Cough * Immune

Answer 213

**36%** - Experimental infection of COPD patients with rhinovirus induces bacterial infection ## Footnote *Coinfection causes greater decline in lung function and prolonged hospital stay*

Answer 214

* *Groundglass opacity** surrounding a *pulmonary nodule/mass, representing haemorrhage* * *- Typically in fungal infection** * *- May represent neoplasm or vasculitis**

Answer 215

Use of bronchoscopy in immunocompromised: * diagnosis in 65% * sensitivity 75% and spec 86% * 80% accuracy

Answer 216

Found in the **cell wall of aspergillus** - antigen can be done in BAL or blood. Better in BAL - Sens 79%, spec 86%, accuracy 89% * Get false positives in - contamination - tazocin, amoxicillin, plasmalyte* Corss sensitive with: - penicillium, alternari, cladosporium, trychphyton, histoplasmosis, cryptococcus * *Get false negatives with antifungal treatment** - sens 52% vs 89%

Answer 217

* Bronchiectasis that spares the peripheries * Mosaic attenuation

Answer 218

Oestradiol levels are related to **alginate production of pseudomonas** * *- testosterone not, placed on OCP not* **Exacerbations correlat**e with the cycle phase in patients with **cystic fibrosis**

Answer 219

CV risk begings to climb around 30 events/hr

Answer 220

* Honeycombing * Traction bronchiectasis * Reticulation

Answer 221

FVC trends predict mortality better than other parameters 10% change in FVC or 15% in DLCO is considered significant 6MWT has no role in measuring change in disease severity

Answer 222

Not indicated in the majority - Most importantly to exclude hypersensivity pneumonitis

Answer 223

Describes a **histopathological pattern on biopsy** * *- heterogeneity!** - hallmark is **fibroblastic foci** (demonstrate ongoing damage) Also used to describe a **radiological pattern on HRCT.** **Especially absence of groundglass** **Causes** * IPF * Asbestosis * CT related ILD

Answer 224

Different prognosis and treatment options Basically if IPF and appropriate to should refer for transplant

Answer 225

NOT a CURE, slows down decline of RFT but minimal QoL benefit

Answer 226

RCT for nintedanib

Answer 227

**ILD** with **features of CTD** that don't meet specific classification criteria for a given autoimmune disease

Answer 228

**Early** * Pneumonia very common. 66% in one series * Given prophylactic broad spectrum antibiotics in the initial days * Mediastinitis more common than in cardiac transplant **Middle** * Incidence of CMV 75-100% if either donor or recipient is seropositive * Most severe in cardiac and lung transplant for unknown reasons * High incidence of HSV pneumonitis **Late** * PCP incidence high in lung and cardiac transplant

Answer 229

**Glycoprotein** in the family of serine **protease inhibitor**s, controlling inflammatory cascades * Produced in hepatocytes Inherited in an **autosomal co-dominant pattern** **Phenotypes** * Normal * Normal alleles are classed M, normal genotype = MM/PiMM * Deficient * Plasma AAT \<35% of normal * Most common deficient allele associated with emphysema is Z, carried by 2-3% of Caucasians * Null * No detectable AAT protein * Least common, highest risk of lung disease, no risk of liver disease * Dysfunctional * Produce a normal quantity of protein that is defective * Z and M(malton) the two common ones Hepatic Disease * Chief cause of liver disease in children * Z and M(malton) alleles most well known to confer risk, autosomal recessive * Due to accumulation of dysfunctional AAT protein in the hepatocyte, seen as intrahepatocyte inclusions with +ve acid Schiff stain * 10-15% of newborns and adults develop hepatic disease * Most are PiZZ **Pulmonary Disease** * **Loss of function and imbalance between neutrophil elastase and the elastase inhibitor AAT.** Protects against proteolytic degradation of elastin * Cigarette smoking and infection increase **elastase production,** therefore greatly increase risk of progression * Polymers of Z antitrypsin are chemotactic to neutrophils * Deficiency = early onset emphysema. * **Bullous changes more prominent in bases than apices**. Can be apical or diffuse in 1/3 * Test in **persistent obstruction despite bronchodilator,** *early onset emphysema in non-smoker, and family history of emphysema/liver disease* **Other** * Necrotising panniculitis; vasculitis, psoriasis, urticarial, angiodema * Aneurysms and arterial fibromuscular dysplasia * IBD * GN * ANCA +ve vasculitis

Answer 230

* Systemic vasodilation resulting in **V/Q mismatch** * **Presentation** * orthodeoxea: decreased O2 saturation when upright, increased when lying * platypnoea: dyspnoea when upright, better when lying flat * Above due to dilation resulting in worsening of V/Q mismatch when sitting upright (blood pools to poorly ventilated bases)

Answer 231

* Clear growth = resect * Groundglass = annual CT (higher risk of malignancy but usually slower growing) * Stable over 2yrs without groundglassing = discharge * PET in \>=1cm with intermediate risk. Sensitivity 95%, specificity 75% High risk features * age \> 60, current smoker, corona radiata or spiculated nodule margins * volume doubling of mass 20-100 days, upper lobe calcification, spiculation. What features carry the highest likelihood ratio of malignancy? * \>16mm cavity wall thickness * spiculated edge * Age \> 70 * size \> 3cm * History of other malignancy * Smoking \> 40 ciggs/day What carries a 0 likelihood ratio of being malignant? * growth \< 7 days and no growth \> 465 days * benign pattern of calcification

Answer 232

Mutation present in **15% of lung adenocarcinoma** * **Women**\>men * **Non-smokers**\>smokers * **Asian**\>non-asian EGFR TKIs approved for 1st line treatment of EGFR +ve NSCLC - shown to be equivalent to chemotherapy 1st generation: erlotinib, gefitin and 2nd gen Afatinib * **Acne**, diarrhoea, rare: pneumonitis/hepatitis 3rd generation: osimertinib (less rahs, designed for drug resistance)

Answer 233

Paradoxical movement of the abdomen inward with inspiration **Bilateral** -\> has **mod-sev restriction of TLC** This gets **worse on lying down** - **decrease in VC of 30-50% when supine supports the diagnosis**

Answer 234

**CO2 and acidosis** preferentially stabilise the deoxygenated form of haemoglobin, resulting in **release of oxygen from haemoglobin** This is **desirable in the tissues**

Answer 235

* *Bone morphogenetic protein receptor type-2 (BMPR2)** - BMPR2 inhibits smooth muscle proliferation and induces apoptosis - abnormalities -\> proliferation of pulmonary vascular cells -\> remodelling - mutation confers 15-20% chance of developing PAH during lifetime - accounts for 70-80% of familial PAH

Answer 236

Sputum culture

Answer 237

Pleural fluid:serum protein \>0.5 Pleural fluid: serum LDH \>0.6 Pleural fluid LDH \>2/3ULN of serum LDH **If all false then transudate** If **\>=1 true** then **exudate**

Answer 238

50% at 5yrs 75% at 10yrs Major impediment to long term graft and patient survival Hard to demonstrate on transbronchial biopsy - decline in FEV1 used as a surrugate marker Risk factors - acute rejection the major one - GORD or silent aspirations may contribute in some Retransplant the only definitive management - systemic immunosuppression doesn't really work - aerosolised cyclosporine has shown potential efficacy - fundoplication to control reflux has been associated with improved PFTs in some with BOS

Answer 239

Virtually all have **long-standing atopic asthma** Classically in **4th-5th decade** - chronic asthma, recurrent pulmonary infiltrate, and bronchiectasis - long Hx of intermittent wheezing with evolution into more chronic and symptomatic: fever, chills, pulmonary infiltrates, productive cough * *Segmental infiltrate or atelectasis in the upper lobes** - branching, f**inger-like shadows** of mucoid impaction of dilated central bronchi are pathognomonic.

Answer 240

**Rare condition characterised by alveolar accumulation of surfactant** * several causes * *Autoimmune in 90%** - antibodies against **GM-CSF -\>** no activation of alveolar macrophages -\> accumulation of surfactant * *Presentation varies considerably** - everything from asymptomatic and spontaneously remiting to severe respiratory failure * *HRCT** * - crazy paving pattern* * *Lavage** * - grossly turbid exudate - periodic acid-Schiff positive* **Whole lung lavage the most effective therapy**

Answer 241

**Occurs in ~30% of women with tuberous sclerosis** * TSC1 encodes hamartin, TSC2 encodes tuberin Sporadic LAM also associated with mutation of tuberous sclerosis genes Characterised by smooth muscle cell infiltration and cystic destruction of the lung * express markers of smooth muscle and melanocytic differentiation **Presentation** * progressive SOBOE, recurrent pneumothoraces, abdominal/thoracic lymphadenopathy, abdominal tumours * angiomyolipomas, lymphangiomyomas May present with just abdominal disease, mimicing lymphoma/ovarian cancer * very rare **_Rx: sirolimus_**

Answer 242

* Most sensitive for the main and lobar pulmonary arteries * decreases in the segmental and sub-segmental vessels * Normal V/Q rules out pulmonary hypertenion due to chronic thromboembolic disease

Answer 243

Variable intrathoracic obstruction

Answer 244

**Type 1 = squamous** * cover **90-95%** of alveolar surface * involved in **gas exchange** * *unable to replicate, susceptible to toxic insults* **Type 2 = surfactant secreting** * **\<5%** of alveolar surface * can divide and differentiate into type 1 cells if lung tissue is damaged

Answer 245

**PaO2** usually remains near normal until **FEV1 \<50% predicted** * *ventilation-perfusion mismatching accounts for essentially all of the reduction* **PaCO2** usually not elevated until **FEV1 \<25%** * may not even occur then

Answer 246

* *Upper (think allergens)** - hypersensitivity pneumonitis - coal worker's pneumoconiosis (+ progressive massive fibrosis) - silicosis - sarcoidosis - tuberculosis - histiocytosis - ankylosing spondylitis (rare) * *Lower (think immune and drug)** - IPF - CTD related - Drug: amiodarone, bleomycin, methotrexate - Asbestosis (fibres are heavy)

Answer 247

* Abscess * s aureus, klebsiella, pseudomonas * Squamous cell lung cancer (others can do but less common) * Tuberculosis * Granulomatosis with polyangiitis (GPA, Wegener's) * Rheumatoid arthritis * Other infection * aspergillosis, histoplasmosis, coccidiodomycosis

Answer 248

* **Primary ciliary dyskinesia** * respiratory tract (including eustachian tube and inner ear), fallopian tube, flagella of sperm = infertility * Rare autosomal recessive disorder resulting in defective outer/inner dynein arms (give cilia motility) * Only known as **Kartagener's when associated with situs inversus** * ~50% of the time

Answer 249

**Descent** is a required part of management of all Acute mountain sickness * generally self limiting * headache, nausea, fatigue * starts above 2500m, develops gradually over 6-12hrs, may last days * acetazolamide to prevent, gain altitude at \<500m/day High altitude pulmonary oedema * classic **pulmonary oedema** features * nifedipine, dexamethasone, acetazolamide, PDE5 inhibitors * oxygen if available High altitude cerebral oedema * dexamethasone

Answer 250

Dipalmitoyl phosphatidylcholine

Answer 251

Crocidolite (blue)

Answer 252

Usually patients have either disorder predominating * as they have dissimilar physiologic effects * emphysema: reduced recoil, increased compliance, increased volumes, reduced maximal exp flow * fibrosis: increased recoil, decreased compliance, reduced volumes, normal/increased maximal exp flow **Features** * male (90%), smoking history (98%), dyspnoea, pulmonary hypertension * upper lobe emphysema * lower lobe fibrosis, predominance of UIP * relatively normal spiro/lung volumes with severely impaired DLCO **Diagnosis** * consensus definition doesn't exist * HRCT showing typical features + above hx/RFs **Complications** * pulm HTN more frequent and severe than in IPF alone * significantly increased risk of lung cancer, with worse outcomes if they get it **Prognosis** * median survival 2-8yrs * if pulmn HTN 1yr survival 60% * seem to have similar outcomes to pulm fibrosis alone **Management** * smoking cessation * lung transplantation the only definitive

Answer 253

Viral * - coronavirus, rhinovirus, influenza Bacterial * - haemophilus influenzae * - moraxella catarrhalis * - staph aureus * - pseudomonas aeruginosa * - strep pneumoniae

Answer 254

High calorie, high fat * used to be low fat to reduce steatorrhoea * now recognised important to get enough fat intake Supplementation with vitamin A, D, E, K 90% need pancreatic enzymes

Answer 255

Beta carotene and vitamin E

Answer 256

Within **1 week of a known insult**, or new/worsening respiratory symptoms **Bilateral opacities** not explained by effusions, collapse/consolidation, nodules **Hypoxia not explained by CCF or overload** * do a TTE in those with no risk factors for ARDS to look at LV function **Phases** * acute exudative phase * fibrosing alveolitis (days to weeks after) * recovery phase **Management** * **low volume** ventilation (6mL/kg ideal bodyweight) * **prone ventilation decreases mortalit**y (PROSEVA study NEJM 2013; 23.6% vs 41% 90 day mortality proning 16hrs/day vs not) * **supportiv**e care * nothing works to fix it

Answer 257

Not synonymous with asthma * lacks airway hyperresponsiveness * have the same frequency of atopy as the general population Causes a **steroid responsive** chronic cough * responds to oral or ICS Diagnosed with **\>2.5% eosinophils** in induced **sputum**

Answer 258

**Summary** * **LABA/LAMA \> LABA/ICS** * Fewer exacerbations in the LABA/LAMA group LANTERN study in Int J Obstruct Pulm Dis 2015 * looked at the same population with \<=1 exacerbation in the last 12 months * showed non-inferiority

Answer 259

* *BODE** Index - higer the score the worse prognosis - Better predicts mortality, hospitalisation, survival post LVRS * *BMI -** \< 21 = 1 point * *Obstruction -** FEV1 * *Dyspnoea -**on dyspnoea scale score * *Exercise -** distance walked in 6 minutes

Answer 260

Also known as **Hamman-Rich syndrome** Rapidly progressive non-infectious ILD * the only acute process of the idiopathic interstitial pneumonias * effectively looks like and follows a similar course to ARDS Typically occurs in middle aged adults without pre-existing lung disease * presents with productive cough, fever, dyspnoea that often requires mechanical ventilation within weeks of onset Radiology - same as ARDS

Answer 261

PESI useful to identify low risk patients suitable for outpatient management **Imaging** * RV dysfunction due to PE = 2x mortality * RV thrombus = ~doubled mortality * Co-existent DVT = 2x mortality **Laboratory** * low BNP predicts uncomplicated course * raised troponin OR 5 for short term mortality * hyponatraemia \<130 OR 3 for mortality * lactate \>2 predicts mortality

Answer 262

Routine screening for those presenting with VTE not recommended **Family history +ve** * 1st degree relative with VTE \<45yrs * *protein C, S, antithrombin III deficiency, factor V leiden, prothrombin gene mutation* **Family history -ve** * \<45yrs and recurrent VTE = *thrombophilias and APLS* * thrombosis in multiple or unusual sites **(portal\*, hepatic\*, mesenteric, cerebral veins) = *thrombophilias*** *and **APLS*** * warfarin induced skin necrosis = look for protein C deficiency (rarely protein S or FVL) * arterial thrombosis = look for APLS \* = also test for **JAK2 mutation and PNH**

Answer 263

BMI \>=40 or weight \>120kg - lack of data to guide dosing

Answer 264

PE with hypotension ('massive') = thrombolyse * RR 0.20 for mortality * 9.4% vs 19% risk of recurrent VTE or death PE **without hypotension = don't thrombolyse** * no difference in mortality PE without hypotension but with RV dysfunction and elevated troponin ('submassive') = not standard * no difference in mortality (Meyer et al NEJM 2014) * reduced cardiovascular collapse but increased bleeding

Answer 265

Poor prognosis - male - CTD - older - NYHA class

Answer 266

* *Endothelin-1 has A and B receptors** - levels increased in plasma and lungs in PAH - levels correlate with disease activity and mortality Both present **on smooth muscle** * activation -\> **vasoconstriction** **Endothelin B** present on **vascular endothelium** * activation -\> **NO release** and **vasodilation**

Answer 267

* FBE + immunoglobulin level * Culture of airway secretions, including for non-tuberculous mycobacteria * if first isolation of pseudomonas attempt eradication * Spirometry * Serological tests for aspergillus

Answer 268

* *Routine sputum MCS 3 monthly to guide therapy** - base antibiotic choice on prior isolates with exacerbations * *Pseudomonas aeruginosa** - initial isolation -\> attempt to prevent colonisation with aggressive antibiotic therapy - \>70% of adults chronically infected, once mucoid phenotype develops impossible to eradicate - mucoid -\> worsening lung function - in chronic infection antibiotic susceptibility doesn't affect outcome - chronic azithromycin beneficial (decreases exacerbations, increases FEV1) - contact precautions and masks for healthcare workers; patients shouldn't congregate together * *Burkholderia cepacia complex** - chronic infection -\> accelerated decline in lung function - usually multi drug resistant - contraindication to lung transplantation (due to worse outcomes) * *Non-tuberculous mycobacteria** - MAC not associated with worse transplant outcomes - Abscessus associated with worse transplant complications - only treat is symptoms, worsening lung function, or nodular infiltrates/cavitating disease * *Antibiotics** - one antibiotic for each organism isolated on culture - two antibiotics if possible for each gram -ve isolated - no role for routine tune-ups - no role for chronic/cyclical antibiotics other than azithromycin

Answer 269

* Smoking within minutes of waking predicts stronger dependence * Increased number of cigarettes smoked per day predicts stronger dependence

Answer 270

* *Primary =** no underlying lung disease. Recurrence 25-50% - Smoking the biggest: \>22cpd -\> 102x RR; \<12 cpd 7x RR - FHx in 10% - others: Marfan's, homocystinuria, thoracic endometriosis * *Secondary =** underlying lung disease. Recurrence \>50% (depends on aetiology) - usually more dangerous than PSP due to decreased reserve. M**ortality 16% - COPD responsible for 50-70%** - 5-10% of PCP will get SSP - up to 20% of CF \>18yo will develop SSP - others: TB, lung cancer, necrotising pneumonia, ankylosing spondylitis, LAM, ILD, histiocytosis, CTD * *Management** (**_2cm_** (at the level of hilum) the cutoff for small vs large; symptoms more important than size) - SP of any size with significant dyspnoea -\> active intervention - SSP of any size should be intervened upon (only 60% spontaneously close) - needle aspiration equivalent to large bore + reduced admission rates and LOS - never repeat needle aspiration unless technical difficulties caused it to fail (insert small bore drain rather than repeat)\ * *Recurrence prevention** - thoracotomy + pleurectomy -\> 1% recurrence - VATS pleuradesis -\> \<5% recurrence - Talc pleuradesis -\> 5-8% recurrence + 2% risk of ARDS - smoking cessation

Answer 271

RAPID score

Answer 272

RCT of **5 days vs 14 days of 40mg prednisolone** in those presenting with acute exacerbation of COPD - 314 patients, 92% admitted to hospital **5 days non-inferior to 14 days** * - predefined non-inferiority criterion was upper limit of 15% increase in re-exacerbation rates * - no difference in time to death; combined exacerbation, death, or both; recovery of lung function

Answer 273

Phenotype is distinct as some with COPD are prone to frequent exacerbations * - Generally defined as **\>=2 exacerbations per year** Rate of exacerbation in the past year predicts risk in the next year Frequent exacerbations lead to more rapid decline of lung function, more rapid functional decline, greatest risk of AMI Targets for interventions to reduce exacerbations * - LAMAs reduce exacerbations, most data for tiotropium * - LABA/LAMA superior to LABA/ICS for exacerbation prevention * - indacterol, vilanterol, olodaterol superior to salmeterol * - add ICS in those with significant reversibility or frequent exacerbations * - pneumonia risk least with budesonide

Answer 274

Those with both are more likely to have pulmonary hypertension or hypercapnoea than with either alone **OSA (untreated) in those with COPD predicts worse survival and severe exacerbations** * - risk abolished by treatment of the OSA

Answer 275

HIGH FLOW BETTER! - less required intubation at 28 days - decreased rates of death at 90 days

Answer 276

RCT of addition of tiotropium vs placebo in those with poorly controlled asthma on ICS/LABA * 912 patients Outcomes **(improves PFTs, symptoms, exacerbations)**

Answer 277

**Asthma** * - eosinophilic and TH2 driven **COPD** * - neutrophilic and CD8 driven **Note that there's an overlap** * - longstanding asthma can move toward a neutrophil/CD8 predominance * - a portion with COPD have TH2 pathway and eosinophils

Answer 278

**Involve all with COPD early, even with mild symptoms** **Grade A evidence** * improves exercise capacity * reduces breathlessness * improves health related QOL * reduces hospitalisations and LOS * improves recovery after hospitalisation for an exacerbation * reduces anxiety/depression associated with COPD **Grade B evidence** * benefits extend well beyond immediate period of training * improves survival * enhances effect of LABA

Answer 279

* Progressive respiratory failure - 39% * Cardiovascular disease - 24% * RV hypertrophy, cor pulmonale due to PH+RHF, LV due to concurrent IHD * Bronchogenic carcinoma - 10% * 14:1 excess risk c/w general population * same histologic distribution as the general population * Pulmonary embolism - 3-7% * Pulmonary infection - 2-4% * Pneumothorax * less often than in other ILDs * Complications of therapy * Referral for transplant * should be referred early if appropriate * DLCO \<40%, FVC \<80%, any dyspnoea or functional limitation due to IPF, decrease in sats to \<89% even if only during exertion * decline in FVC \>=10% or DLCO \>=15% during 6 months of f/u, pulmonary hypertension

Respiratory Flashcards

(354 cards)