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RespNET clinic aide memoire: ILD. August 2015
Interstitial lung disease
General
ILDs or DPLDs are a heterogenous group of diseases, with common features of non-infective infiltrates of the
interstitium and alveoli. They generally present with breathlessness, restrictive lung function and reduced TLCO.
History
Usually patients have a chronic history of dyspnoea and cough for months prior to attendance at chest clinic. Can be
acute < 3 weeks, or episodic. Documentation of exercise tolerance on the flat and ability to manage stairs is a useful
marker of severity.
Cough
invariable in sarcoidosis, hypersensitivity pneumonitis (HP), cryptogenic
organising pneumonia (COP), and idiopathic pulmonary fibrosis (IPF).
Wheeze
an airway-centred symptom which might suggest Churg-Strauss or
eosinophilic pneumonia (or co-existent other diagnosis).
Pleurisy
suggestive of connective tissue disease (rheumatoid, SLE), asbestosrelated or drug-related disease.
Haemoptysis
might indicate pulmonary haemorrhage (Wegener’s or Goodpastures),
or an associated lung cancer, pneumonia, or pulmonary embolism.
Rheumatological may point to underlying rheumatological diagnosis: Raynaud’s,
symptoms
thickenend skin, dysphagia, gastro-oesophageal reflux, arthralgia,
rashes, ocular symptoms, sicca symptoms, myalgia, proximal muscle
weakness. There may also be constitutional symptoms (fever, malaise,
weight loss).
Haematuria
might suggest an underlying vasculitis
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Smoking history is important as smoking is an independent risk factor for IPF. Some rare interstitial lung
diseases (ILD) occur almost exclusively in smokers (Respiratory Bronchiolitis Interstitial Lung Disease: RBILD,
desquamative interstitial pneumonia: DIP, and Langerhans Cell Histiocytosis: LCH), whilst smokers are less
likely to have HP or sarcoidosis.
History of previous occupation(s), environment and hobbies should evaluate exposure to dusts, asbestos, or
antigens, and use of respiratory protection.
Family history is occasionally relevant, as both IPF and sarcoidosis can be (rarely) familial.
Travel history may suggest possible parasitic infestation, which may be associated with eosinophilic lung
disease.
HIV risk factors or possibility of immunosuppression should be considered since acute ILD can represent
opportunistic infection.
Past medical history of chemo- or radiotherapy might be the basis for drug-induced or radiation-induced
fibrosis. Radiation fibrosis usually develops within weeks or months of exposure but sometimes occurs years
later.
Drugs may cause pneumonitis/fibrosis: nitrofurantion, sulphasalazine, methotrexate, gold, penicillamine,
leflunomide, etanercept, amiodarone, statins, ACE inhibitors, bleomycin, cyclophosphamide, EGFR-inhibitors
(e.g. tarceva), heroin, methadone, talc, aspirin, interferons. Check pneumotox.com for others.
Examination
 Finger clubbing suggests IPF, asbestosis, chronic HP, or rheumatoid-associated ILD. Clubbing is rarely
observed in polymyositis/dermatomyositis-associated ILD or sarcoidosis.
 Fine basal inspiratory crackles are heard in >90% of cases of IPF, but may also be heard in connective tissue
disease-associated ILD and asbestosis. Crackles are usually absent in sarcoidosis. Inspiratory squeaks are
heard in bronchiolitis and subacute HP.
 Wheeze may indicate asthma with Churg-Strauss, eosinophilic pneumonia, or bronchiolitis.
 Sarcoidosis is often manifest by lymphadenopathy, hepato-splenomegaly, uveitis, and skin rashes.
 Pulse oximetry should be undertaken to evaluate hypoxia. Chronic hypoxia may be associated with clinical
signs of right heart strain or failure
RespNET clinic aide memoire: ILD. August 2015
Investigations
For all patients:
 FBC, U&E, LFT, Bone profile, CK, ESR and CRP, Rheumatoid factor and ANA
o If ANA raised: lupus anticoagulant and anticardiolipin Ab.
o ENA (Ro, La, RNP, Scl-70, Jo-1, Sm). Note disease associations: Scl-70 in diffuse cutaneous
scleroderma (SSc)and SSc-associated ILD; anti-centromere pattern of ANA in limited cutaneous SSc
with pulmonary hypertension; anti-Jo-1 in Dermatomyositis/ Polymyositis and Inflammatory
myopathy
 Urine microscopy (vasculitis)
 Spirometry, lung volumes, and gas transfer TLCO
 CXR
 HRCT scan (if diagnosis not obvious after CXR)
 6MWT (desaturation on 6MWT at presentation indicates poorer prognosis)
In individual cases, where relevant:
 ECG (conduction block may occur in sarcoidosis)
 24h Urine calcium (sarcoid)
 Serum ACE (if sarcoidosis suspected)
 ANCA (if vasculitis suspected)
 Precipitating antibody (precipitins - IgG) to suspected antigen (e.g. avian precipitins in suspected pigeonfanciers lung
 Bronchoscopy (decision to bronch should be made by MDT)
o Bronchoalveolar lavage
 To exclude infection
 To characterise inflammatory cell profile:
 Sarcoid:
-elevated neutrophils and lymphocytes
-elevated CD4/CD8 lymphocyte ratio
 HP:
-elevated lymphocytes
-reduced CD4/CD8 lymphocyte ratio
o Transbronchial lung biopsy (decision to biopsy should be made by ILD MDT) – cryogenic biopsy now
available in specialist centres. This may avoid the need for surgical lung biopsy (open or VATS)
which should be considered whenever diagnosis is not certain from the clinical features and
radiological appearances. This should be an MDT decision.
 For bronchocentric ILD
 Sarcoidosis (should also take endobronchial biopsy and/or EBUS)
 COP
 Alveolar proteinosis
 Echocardiogram (transthoracic) – for pulmonary artery hypertension (PAH)
o Consider if dyspnoea or TLCO disproportionate to parenchymal lung disease
o Consider referral to a tertiary pulmonary hypertension centre if systolic pulmonary artery pressure >
50mm Hg
Treatment
Patients with ILD should be discussed in an MDT setting
IPF (Idiopathic Pulmonary Fibrosis - usual interstitial pneumonia: UIP and fibrotic- non-specific interstitial
pneumonia: NSIP)
 Usually >45yrs with persistent progressive breathlessness and cough
 Poor prognosis – median life expectancy 2.9-5 years (but 20% survive >5yrs).
 Assess for pulmonary rehabilitation (incl symptoms, QoL assessment, 6MWT or similar)
 Assess for long-term (criteria as for COPD), ambulatory, and palliative oxygen therapy
 Consider oral opiates for intractable cough (e.g. MST 5-10mg bd, esp in end-stage disease)
RespNET clinic aide memoire: ILD. August 2015
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Treat symptomatic gastro-oesophageal reflux. Reflux may play a role in pathogenesis and progression
Consider potentially disease-modifying therapy in patients with severe disease at presentation or
progressive disease. Assess response to therapy (clinical and physiological : FVC and TLCO at 3 month
intervals). Pred + Azathioprine + NAC no longer recommended. NAC is still used by some in clinical practice.
o Pirfenidone (if FVC 50-80% predicted) – NICE approved, on patient access scheme. Stop if FVC falls
by 10% in 12months.
Consider enrolment into clinical trials (current list on clinicaltrials.gov):
o Nintedanib
o Lebrikizumab
o Other monoclonal antibodies and immune modulators
Consider referral for lung transplant if age < 65, and disease advanced (TLCO < 40%) or progressive ( >10%
fall in FVC or >15% fall in TLCO over 6 months). Assessment process is lengthy so refer early if patient wishes
to pursue and no exclusion criteria
Consider best supportive care with pro-active advance care planning
Follow-up appointments for IPF
 Support smoking cessation pro-actively (including pharmacological support)
 Reassess lung function, sats (? Oxygen therapy criteria met), symptoms
 Reconsider pulmonary rehabilitation if not completed
 Reconsider whether should refer for transplant (assess against criteria)
 Assess psychological needs and refer for psychology input as necessary
 Assess for comorbidities (may include anxiety, bronchiectasis, depression, diabetes, dyspepsia, ischaemic
heart disease, lung cancer and pulmonary hypertension)
 Consider advance care planning and referral to palliative care (particularly if chronic disabling breathlessness
– fans, opiates, pacing techniques, advance care planning, psychological support of patient and carer)
CPFE (combined pulmonary fibrosis and emphysema)
 increasingly recognised - characterised by exertional dyspnoea, upper-lobe emphysema and lower-lobe
fibrosis, preserved lung volume and severely diminished capacity of gas exchange.
 CPFE typically occurs in male smokers, and the mortality associated with this condition, particularly if PH is
present, is significant. May prompt earlier involvement of palliative care
 Requires treatment of both conditions (with smoking cessation as number 1 priority)
COP (Cryptogenic Organising Pneumonia)
 Typical COP associated with good prognosis. Fibrosing COP more variable.
 Prednisolone 0.75-1mg/kg prednisolone daily. Wean over 6-12 months. (No RCTs to backup this regime)
 Commonly relapses (usually at doses Pred <20mg/day) but rarely associated with poor outcomes
 Various immunosuppressants used in refractory cases: azathioprine, cyclophosphamide, cyclosporine
RBILD (Respiratory-Bronchiolitis Interstitial Lung Disease)
 RB is physiological response to smoking and may be present 3yrs after quitting. RB-ILD is more severe
reaction in minority of smokers, with evidence of ILD, lung function impairment and symptoms
 BAL may help distinguish from HP (main differential on HRCT)
 Smoking cessation is primary treatment. No other interventions known to be beneficial
 No evidence of benefit of corticosteroids
DIP (Desquamative Interstitial Pneumonia)
RespNET clinic aide memoire: ILD. August 2015
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Rare, usually 40-50yr old smokers, M > F. Finger clubbing in 50%.
Lower zone ground glass on HRCT. Difficult to distinguish from RBILD, HP or sarcoidosis on imaging or
BAL so biopsy often needed to make definitive diagnosis
Smoking cessation is primary treatment
Prednisolone 20-60mg/day has been shown to be beneficial. Not clear how long to treat for. Relapses on
stopping may respond to restarting. Small numbers have received azathioprine/ cyclophosphamide
LIP (lymphoid-interstitial pneumonia)
 Rare. Crossover with B cell MALT – requires biopsy and specialist immunohistochemistry to distinguish
 Associated with hypogammaglobulinaemia, particularly SCID, and rheumatic/autoimmune diseases. Also
HIV - AIDS defining disease in children
 Trial of corticosteroids (no evidence for dose or duration)
HP (Hypersensitivity Pneumonitis)
 Acute vs subacute vs chronic
 Acute and subacute show micronodules, midzone ground glass, and air-trapping. Chronic more fibrotic
 Main focus of treatment: antigen identification and avoidance (tricky when 25% exposure not identified)
 Corticosteroids for severe or progressive disease: e.g. prednisolone 40-60mg od for 1 month then taper
over several months. May need steroid-sparing agents if treatment prolonged
 If exposure in work environment refer to occupational lung disease specialist
Connective tissue disease-associated ILD
 Treat severe or progressive disease: prednisolone 0.5-1mg/kg/day for 1 month then taper to 10mg/day
or less. Consider using in conjunction with oral cyclophosphamide or azathioprine
 If assoc with polymyositis or dermatomyositis earlier treatment required to prevent progression
 In SSc-associated ILD, recommended treatment is low dose steroid (prednisolone 10mg od) and/or
cyclophosphamide. High dose prednisolone (>10mg) risks renal crisis.
 Recommended that care is delivered in parallel with Rheumatologist, ideally in a specialist joint
clinic/service
 Patients with connective tissue disease-associated ILD and PAH should be anticoagulated
Sarcoidosis
 High spontaneous remission rate, so treatment often not required
 Treat progressive pulmonary disease (defined by radiology, lung function and symptoms)
 Treat cardiac-, neuro-, and sight-threatening ocular sarcoidosis, hypercalcaemia, lupus pernio, splenic,
hepatic or renal sarcoidosis in association with appropriate organ specialist
o Prednisolone 0.5mg/kg day for 4 weeks then reduce to symptom-controlling maintenance dose
for 6-24 months.
o Use bisphosphonate
o Consider methotrexate as the steroid-sparing agent of choice, if needed
o Consider referral for transplant in end-stage disease
With thanks to Dr Robin Johns for the original version of this clinic aide memoire.