Pulmonary Hypertension
Onset &
Presentation
Investigations
Risk factors
Aetiology
Management
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Symptoms non-specific but severe
suspect in unexplained progressive dyspnoea, fatigue, or syncope
symptoms of CTDs (esp. scleroderma), copd, LV failure
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Exam → signs of chronic lung disease, congenital heart disease, CTD, DVT
CXR (abnormal in 90%) → RV dilation, builky PA with distal ‘pruning’
ECG – signs of R- strain or hypertrophy in up to 90%
screening ECHO for high risk (lcSSc, HIV, congenital heart, sickle cell,
hereditary hemorrhagic telangiectasia, portal HTN) or based on Sx
o probability using TR jet velocity (TRV) and estimate pulmonary
artery systolic pressure (ePASP)
o assessment of RV size, wall thickness, and function
o potential contribution of left-sided heart disease to PH
HRCT, PFTs (↓DLCO to ~ 50%) and 6MWT (sats drop > 10% → 3 x mortality)
V/Q scanning
R-heart study (confirm Dx, severity, reversibility)
o Pressures
 mPAP >20mmHg mild
 mPAP 30 – 45 mmHg moderate
 mPAP ≥45 mmHg severe
o detect shunt
o ensure PCWP < 18 mmHg (ie not Class 2)
o calculate PVR (normal = 1.7 mmHg / L / min)
appetite-suppressing drugs (fenfluramine and phentermine)
tyrosine kinase inhibitors
amphetamines
chronic heart and lung conditions
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5.
PAH (drugs/toxins, hereditary, CTDs, portal HTN, haemolysis, HIV, schisto)
LEFT HEART DISEASE
HYPOXIA
CHRONIC THROMBOEMBOLIC
MISCELLANEOUS (MPNs, vasculitis, infiltrative, CKD5)
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1. PAH
 endothelin receptor antagonists - Bosentan and ambrisentan - block
Endothelin-1 (available only for class III Sx and RA pressure > 8 mmHg)
 iloprost - Prostacyclin analogue – inhaled or IV
 Sildenafil
 young pt, unresponsive disease, R- failure → heart–lung, double-lung
transplant (PAH does not recur but prognosis reflects NYHA-WHO class)
o class I–II (6 years); class III (2.5 years); class IV (6 months)
2. 3. 4. 5. → treat underlying process (Eisenmenger’s repair not usually
possible once reversal of shunting has occurred → heart and lung transplant)
(General measures = continuous oxygen, diuretics, digoxin, spironolactone)
Complications
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aware
screened
present
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Untreated → poor survival rate: 2–3y from the time of diagnosis.
R-heart failure
Functional Impact narrative
Sarcoidosis
Onset &
Presentation
– 1/3 present acutely with Lofgren's syndrome = erythema nodosum, bilateral
hilar lymphadenopathy and polyarthritis
- insidious onset associated with organ damage
Pattern of presentation (A.C.A.E.L.S rare)
 Abnormal CXR - asymptomatic hilar adenopathy (30% )
 Constitutional - Fever, weight loss, malaise, cough or dyspnoea (20%)
 Arthralgia (20%)
 Eye symptoms (10%) - blurred vision, excess tears and light sensitivity
 Palpable Lymphadenopathy (5%)
 Skin (5%) - erythema nodosum, plaques, maculopapular, subcut nodules
 Rare: cardiac arrhythmias, hypercalcaemia or cranial nerve palsies
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Investigations
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bloods → lymphopenia & eosinophilia, ↑ ESR, ↑globulin, ↑Ca++and
hypercalciuria
↑ ACE in ~2/3 (DDX = 5% healthy, PBC, leprosy, mycobacteria ,
histoplasmosis and hyperPTHism but not elevated in malignancy)
CXR usually abnormal
(cavitation and effusions rare but may become colonised with Aspergillus)
o Stage 1 Bilateral hilar lymphadenopathy alone (reversible)
o Stage 2 Bilateral hilar lymphadenopathy and pulmonary infiltration
o Stage 3 Pulmonary infiltration without hilar lymphadenopathy
PFTs typical of ILD (↓volumes /DLCO but normal FEV1 / FVC ratio)
Blood gas → mild hypoxaemia
gallium-67 lung scan → diffuse uptake more specific is ↑uptake in…
o lacrimal / parotid glands (panda sign)
o right paratracheal and left hilar areas (lambda sign)
Biopsy (usually bronchoscopic) → non-caseatng granulomas with ↑CD4 on
BAL but not specific (DDx other granulomatous conditions)
Risk factors
Indications for treatment are
 ↑symptoms or worsening lung function
 neurological, renal or cardiac complications
 major eye disease
 severe systemic symptoms (e.g. fever and weight loss)
Management
Prednisone 1 mg / kg for 6/52 then tapered over a few months for 1 year.
Good prognosis ~ 50% develop some mild permanent organ damage
 Hydroxychloroquine may be useful for skin disease
 Patients who require longer treatment may be offered steroid-sparing
drugs, including chlorambucil, methotrexate or azathioprine
 Infliximab may improve lung function if already being treated with steroids
Complications
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aware
screened
present
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dysphagia from hilar adenopathy
abate in pregnancy but then flare up in the postpartum period.
facial nerve palsy, psychiatric disturbances and seizures
nephrolithiasis can result because of hypercalcaemia.
Conduction problems, including complete heart block and ventricular
arrhythmias, occur in about 5% of patients
Cholestatic LFT derangement
Functional Impact narrative
Obstructive Sleep Apnoea (DDx – CSA, cataplexy, narcolepsy, RLS associated Fe++ deficiency)
Suspect in…
 obesity
 hypertension
 fatigue and daytime sleepiness
 excessive snoring (without excessive snoring, CSA more likely)
 unexplained respiratory failure
Onset &
Presentation
Differential diagnosis of daytime sleepiness
 ‘poor sleep hygiene’
 Poor adjustment to shift work
 Use of sedative and stimulant drugs (e.g. sedatives, caffeine, narcotics)
 Depression with or without early morning waking
 Idiopathic hypersomnolence (sleepiness w plenty of sleep without snoring)
 Narcolepsy (uncommon, sudden, unexpected falling asleep)
Epworth sleepiness scale
 normal 3 - 8
 severe 11 – 20
Polysomnogram (severity based on AHI - total number of apnoea/hypopnoea
per night divided by hours of sleep)
Investigations
Examination
 BMI (50% with OSA and most CSA are not obese)
 Respiratory examination usually normal, BP and fundoscopic signs of HTN
 head, neck - Malapatti score - ‘pharyngeal crowding’. Neck circumference
 other causes of OSA (myasthenia, musc dystrophy, acromegaly, hypoTSH)
 central sleep apnoea - autonomic neuropathy (diabetes, Shy–Drager), brain
stem/cord lesions or spinal cord disease
Risk factors & Aetiology
Correct reversible causes
Concomitant diseases (eg cardiac failure, HTN, asthma) treated vigorously
Surgical correction of polyps, enlarged tonsils or macroglossia
Management
Complications
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aware
screened
present
CPAP - ESS > 11 AND > 15 APNOEAS / HOUR (Up to 50% unable to tolerate)
 Reduced sleepiness
 Improved blood pressure
 Improved cognition
 Improved mood, quality of life and driving
CPAP - ESS > 11 AND 5–15 APNOEAS / HOUR
 Improved symptoms
 Improved daytime sleepiness
 No evidence of improved blood pressure
NORMAL EPWORTH SCORE WITH APNOEA → No evidence of benefit
 aggravating factors – alcohol, hypnotics
 aggravates
o angina / arrhythmias precipitated by the hypoxia
o recurrent increase in afterload can precipitate LV failure
o < 10% of patients develop RV failure and pulmonary HTN
o Driving risk and anaesthetic risk
Functional Impact narrative
AR Cystic Fibrosis
Onset &
Presentation
Ix
Presenting Symptoms
 Asymptomatic (90% diagnosed at 4–6 weeks by genetic screening tests)
 Paediatric - meconium ileus, failure to thrive, recurrent LRTI
 Pulmonary symptoms –productive cough, haemoptysis, wheeze, dyspnoea
 Any “complications”
Elevated Cl- sweat test (98%) – pilocarpine iontophoresis on 100 mg of sweat
o > 70 mmol / L diagnostic
o 40–60 mmol / L suggestive
o < 40 mmol / L normal
CBC (anaemia, ↑WCC), LFTs/coags (deficiencies of fat-soluble vitamins DEKA)
Creatinine to guide aminoglycoside dosing
Sputum culture
Spirometry fluctuates with airway inflammation ( FEV1 < 40% = poor prognosis)
CXR
 ↑lung markings (upper lobes) in 98%
 cystic bronchiectatic changes in > 60%
 Mucous plugs in 33% and atelectasis in 10%
 pneumothorax and pleural changes at the site of previous pleurodeses.
Chest CT not routine, but may define focal bronchiectasis for resection
Risk factors & Aetiology - CFTR gene on chromosome 7 (trait in 1 in 25 Caucasians and 1 in 3000
has the condition. It is rare in other races
 Intensive and repetitive physiotherapy
o deep breathing, percussion, postural drainage, PEP techniques
(acapella), and the forced expiratory technique called ‘huffing’
 pneumococcal / influenza vaccination
 dual IV antibiotics for acute exacerbations of pulmonary disease
 tobramycin nebs for Haemophilus (improve lung function and prognosis)
Management  Routine admission to hospital three or four times a year for intensive
physiotherapy and intravenous antibiotics and bronchodilators (a tune-up)
 pancreatic enzyme replacement based on fat content of each meal
 Lung transplant (CF does not recur in transplanted lung)
 DNAase has been proven to be effective both in those with established CF
lung disease and in preventing decline in lung function
 pulmonary - progressive chronic suppuration → bronchiolitis, bronchitis,
pneumonia and eventually bronchiectasis (main determinant of mortality)
 Minor haemoptysis (< 250 mL lost in ~ 60%), major in ~ 7%
 S.aureus and Ps.aeruginosa grow on abnormal bronchial mucus
 cor pulmonale
 Azoospermia (80% women fertile w breastfeeding often successful)
 Heat exhaustion in hot weather – patients with cystic fibrosis can lose large
amounts of salt in their sweat, which sometimes causes problems,
Complications
particularly in the tropics
 Jaundice and variceal bleeding – focal biliary cirrhosis and portal
 aware
hypertension occur occasionally
 screened
 cystic-fibrosis-related diabetes (20% of 18yo and > 50% of 30 yo
 present
 Pulmonary symptoms, nasal polyps and sinusitis
 Gastrointestinal
o Failure to t hrive
o Steatorrhoea / malabsorption 2° to pancreatic insufficiency – 90%)
o diarrhoea and constipation
o rectal prolapse
o abdominal distension and bowel obstruction (defective water
excretion into the bowel)
Tuberculosis
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Onset &
Presentation
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Investigations
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Risk factors &
Aetiology
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weight loss, sweats and fever, cough with purulent and bloodstained sputum, and pleuritic chest pain from pleural lesions or
uncontrolled coughing
trigger for reactivation of previous infection (diabetes mellitus,
old age, HIV infection).
malnutrition, alcoholism or HIV infection
1. What screening has been done on the patient’s family and
friends? Are any of the family also being treated?
Rifampicin
Management
Isoniazid
Streptomycin
Ethambutol
Pyrazinamide
LFTs, flu-like illness
600 mg
Hepatitis, fever,
neuropathy
Ototoxicity, renal
Optic neuritis
Hepatitis
300 mg (↓to 2 - 3 x a
week in CKD)
1 g (not if pregnant)
15 mg / kg
1.5–2 g
Complications
(aware,
screened,
present)
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Functional Impact narrative
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Clubbing; cyanosis and lower lobe crackles (fine, late, inspiratory) make the diagnosis of IPF likely
upper lobe vs lower lobe
signs of associated systemic disease (erythema nodosum , anterior uveitis , sarcoidosis and CTD that would rule
out IPF)
Assess the severity of the disease (signs of pulmonary hypertension).
Look for signs of drug side-effects (especially steroids).
Interstitial Lung disease
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Onset &
Presentation
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Investigations
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Risk factors
Aetiology
very slow onset with no acute phase → IPF
cough, fever, and myalgias over weeks → COP (steroid responsive)
systemic symptoms – (weight loss, fatigue, fever, rash and arthralgia)
→ CTD
pre-existing asthma → EGPA(ask about renal disease)
haemoptysis and renal disease → Goodpasture’s or SLE
occupational history
o mineral dust (silicon, asbestos, coal work pneumocon)
o chemical fumes (nitrogen dioxide, chlorine, ammonia) birds,
mouldy hay/grain → HP
o cotton, flax or hemp dust → byssinosis
restrictive PFTs (obstructive in sarcoid, histiocytosis and LAM)
ABGs → Type 1 failure
CXR may be normal
HRCT
o UIP - basal, subpleural reticular, honeycombing and traction
bronchiectasis
o COP - multifocal airspace opacities
BAL - Lymphocytosis (cf PMN) → granulomatous or drug
Biopsy only proves sarcoid and excludes infection/malignancy
RBILD, DIP, PLCH →strong association with smoking
premenopausal women w Hx of pneumothorax → LAM
medication use
o cardiac (amiodarone, hydralazine, procainamide)
o rheumatological ( MTX, D-penicillamine)
o chemotherapeutic ( busulphan, bleomycin,
cyclophosphamide)
o others (nitrofurantoin, bromocriptine)
a) Known cause
 Occupational
 CTD (PM/DMS, RA, SLE, dcSSc, MCTD)
 drug-induced
b) Granulomatous (HP, Sarcoid, Tb, chronic berylliosis)
c) Idiopathic interstitial pneumonias
 Major IIP
 UIP vs NSIP
 Respiratory bronchiolitis ILD (RBILD)
 COP vs AIP vs DIP
d) Other (PLCH, LAM)
immunocompromised infections also → interstitial opacities on CXR
Management
1. General – vaccines, LTOT, unilateral transplant if appropriate,
remove exposure, stop smoking
2. Steroids in: COP, chemical injuries, HP, sarcoid, and CTDs
 1 mg/kg/day and reduced to 0.5mg/kg/day after 8 weeks
 Measure response with spirometry, lung volumes and DLCO
 maintenance steroids if improving or stabilised
3. Antifibrotics – pirfenidone & nintedanib reduce decline in lung fx
4. Treat any co-morbidities (esp GORD, OSA, pulm HTN)
Complications (aware, screened, present)
Functional Impact narrative
Bronchiectasis
Onset & Presentation
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Investigations
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Risk factors
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Aetiology
Management
Complications
(aware, screened,
present)
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Functional Impact narrative
Onset of cough and sputum production
childhood whooping cough or measles
influenza and adenovirus LRTis
Lung Cancer
Onset &
Presentation
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Investigations
Risk factors
Aetiology
Management
Complications
(aware, screened,
present)
Exam (clubbing, fixed insp wheeze over large bronchus,
Radiology
o CXR /CT scans
 peripheral nodule → adeno
 central with obstruction → squamous
 mediastinal or hilar mass → small cell
 alveolar infiltrate – bronchoalveolar
o PET / CT for metastatic disease
 Bronchoscopy vs thoracoscopy biopsy, sputum cytology
 PFTs for surgery (FEV1 ≥ 1.5 L could tolerate pneumonectomy
& postop FEV1 ≥ 1 L minimum tolerable)
 Smoking
 asbestos (asbestos + smoking synergistic not additive uranium miners)
 chronic scarring (Tb, dcSSc, ILD)
 Adenocarcinoma 32% (5y = 17%)
 Squamous 29% (5y = 15%)
 Small (oat) cell 18% (5y = 5%)
 Large cello 9% (5y = 11%)
 Bronchioalveolar 3% (5y = 42%)
Small cell carcinomas
 limited disease
(ipsi/contralateral hilar, mediastinal and supraclav nodes)
o chemo and concurrent radio improve prognosis
o Prophylactic cranial irradiation if complete responses
o median survival ~ 12–18 months
 extensive disease (contralateral lung, distant metastases)
o median survival ~ 6–12 months
NSCLC
 Stage I - III
o 1/3 sufficiently localised resection (adjuvant cisplatin)
o Otherwise as per Stage IV w better prognosis
 stage IV disease (Chemoradiotherapy )
o non-squamous → pemetrxed-based chemo
o PD-L1 expression ≥50% → pembrolizumab
o adeno → driver mutations
 EGFR → osimertinib, erlotinib, gefitinib
 ALK rearrangements → crizotinib
o Airway obstruction →Nd-YAG laser for palliation.
LOCAL EXTENSION
 Pleura/pericard effusion
 Rib involvement
 Nerve involvement
 SVC/trachea/oesophag
obstruction
 Lymphangitis
Functional Impact narrative
INDICATIONS
COPD – FEV1 < 25% predicted, PaCO2 > 55 mmHg
CONTRAINDICATIONS
Relative
Diabetes
Osteoporosis
Cystic fibrosis, bronchiectasis – FEV1 < 30% or
Alcohol excess
complications (e.g. cachexia, severe haemoptysis)
Still smoking
or PaCO2 > 50 mmHg, PaO2 < 55 mmHg
Likely compliance problems
ILD – progressive symptoms, VC, DLCO < 60%
Atypical mycobacterial
colonisation of lungs
Weight > 130% of ideal or
Pulmonary hypertension – NYHA class III or IV,
< 70% of ideal
pulmonary artery pressure > 55 mmHg, cardiac index Absolute
< 2 L / min
HIV, hepatitis B, hepatitis C
Eisenmenger’s syndrome – severe symptomatic
and liver disease, malignancy,
impairment. The 2-year prognosis is not improved
other organ failure
for these patients
Differential Dx of CNS lesions
Differential Dx of CNS lesions
Instantaneous
Acute
Asthma/COPD
Cardiac
Parenchymal
disease
Subacute
Chronic
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CTDs (SLE/Sjögren’s /Behçet’s )
small vessel ischaemia
acute disseminated encephalomyelitis
meningovascular syphilis
paraneoplastic effects of carcinoma
sarcoidosis
Lyme disease
multiple emboli from any source
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Multiple Sclerosis
Paraneoplastic Limbic Encephalitis (progressive
cerebellar ataxia / movement disorders /psych
CNS neoplasm – symptoms are usually progressive
Vitamin B12 deficiency
CNS vasculitis
SLE – can cause white matter changes on MRI and
encephalopathy
Sarcoidosis
HIV and syphilis
Migraine
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Aspergillus
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MAC
Regardless of AFB smear result, if Sx AND evidence of
pulmonary disease by imaging, infection (vs colonization of
secretions) includes one of:
 +ve culture from ≥2 separate expectorated sputum
 +ve culture from ≥1 BAL
 mycobacterial features on lung biopsy (granulomatous
inflammation or AFB) and +ve culture for NTM
 Biopsy showing mycobacterial features and ≥1 sputum /
bronchial washings culture +ve for NTM
 pleural fluid +ve culture or other normally sterile
extrapulmonary site
 fungal disease, malignancy, and tuberculosis excluded
Haemophilus
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Multiple Sclerosis
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Onset & Presentation
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bloods
CSF for oligoclonal banding
MRI brain and cord - (correlates with morbidity burden
– brain stem / cord cause ↑↑ disability)
o 2 x lesion types
 Gad. leakage into brain from vessels for
months after formation of a new lesion
 T2-weighted images show persisting
changes from oedema, gliosis and
inflamm
o Sites x 6
 Corpus callosum
 Juxtacortical white matter
 Periventricular white matter
 Optic nerve
 Pons, cerebellar peduncles and
cerebellum
 Spinal cord
Visual-evoked responses delayed in 80% → previous
optic neuritis (other evoked modalities not diagnostic)
CT scan may show low-density plaques in white matter
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childhood in temperate latitudes
smoking
family history (7 x increase)
Investigations
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Risk factors
Management
Complications
(aware, screened,
present)
episodes of spastic paraparesis, hemiparesis or
tetraparesis
episodes of limb paraesthesiae (posterior column,
medial lemniscus or internal capsule involvement)
episodes of visual disturbance
Charcot’s triad - episodes of ataxia, dysarthria and
tremor - due to cerebellar or post column
band sensations around trunk or limbs
urinary urgency, incontinence of faeces
less common symptoms, such as:
o vertigo, symptoms of cranial nerve disorders
(e.g. tic douloureux)
o pseudobulbar palsy
o seizures
o psych – ED/depression/mania
5. supportive and symptomatic treatment
6. bed rest with meticulous nursing is vital.
7. Treatment of bladder dysfunction, severe spasticity (e.g.
with baclofen), urgency (e.g. with amitriptyline), tic
douloureux and facial spasm (e.g. with carbamazepine
and physiotherapy) is important.
8. Intention tremor → propranolol or clonazepam.
9. immunomodulation / immunosuppression
Factors that worsen symptoms (H.I.P.E)
 heat (hot baths etc) –Uhthoff’s phenom.
 Infection/fever
 Post/partum state (pregnancy improvs Sx)
 exercise
Functional Impact narrative