Management of AcuteInterstitial Lung Diseases

Objectives: Summary of Interstitial Lung Disease Classification:

Reminder

Case based illustrations to cover ACUTE RespiratoryPresentations in Known ILD Unknown ILD

Common themes in Management

When to refer to ICU

ILD – Interstitial Lung disease

Classification of ILDs and DPLDs

*Desquamative interstitial pneumonia can occasionally occur in non-smokers. ATS, American Thoracic Society; DPLD, diffuse parenchymal lung disease, ERS, European Respiratory Society; ILD, interstitial lung disease. 1. ATS and ERS. Am J Respir Crit Care Med 2002;165:277–304; 2. Travis et al. Am J Respir Crit Care Med 2013;188:733–748.

Image adapted from ATS and ERS, 20021 and ATS

and ERS, 20132

Unknown Causes: Known Causes: Idiopathic Pulmonary

Fibrosis

Idiopathic Non specific interstitial pneumonia

Sarcoidosis

Cryptogenic organising pneumonia

Occupational: asbestosis/silicosis

Environmental: Hypersensitivity pneumonities(pigeons/birds)

Immune: Connective Tissue Disease (RA; systemic sclerosis)

Smoking: DIP and RB-ILD

Drugs: Any!

Is this disease inflammatory or fibrotic?

Inflammation Fibrosis

Idiopathic Pulmonary Fibrosis

SarcoidosisHypersensitivity PneumonitisConnective Tissue DiseaseCryptogenic Organising pneumoniaDrug ILDCellular NSIPSmoking related ILD

CTD – Connective Tissue Disease; NSIP – Non specific interstitial pneumonia; AIP – Acute interstitial pneumonia; DIP – Desquamatous interstitial penumonia; RB-ILD – Respiratory Bronchiolitis Interstitial lung Disease; COP – Cryptogenic organising pneumonia; IPF – Idiopathic Pulmonary Fibrosis; HSP –Hypersensitivity pneumonitis; f – fibrotic; c - chronic

History and Examination very important

Symptoms of Connective Tissue Disease

Reynauds, swollen/stiff joints, Dry eyes dry mouth, lethargy, mouth ulcers, photosensitive rash

Occupational/environmental exposures

Birds; Mould; Hot tub; asbestos

Drug history Any!

www.pneumotox.org

Soft signs of Connective Tissue Disease:

Mechanic hands;

periungal erythema

sclerodactyly

tight skin

telangectasia

Case 1: 67 year old male

3 week history of increasing breathlessness

Reduced exercise tolerance from 200 yards to breathlessness at rest

Cough with yellow sputum

Feeling hot

No chest pain No rigors

PMH:

Idiopathic Pulmonary Fibrosis diagnosed 12 months ago

Hypertension

Previous Myocardial Infarction 5 years ago

Angina well controlled

Medication:

Pirfenidone

Bisoprolol

Aspirin

Ramipril

GTN spray

Ex smoker 40 pack year history

Examination:

SOB at rest

Saturations 88% on air

RR 20/min

Pulse 120 BP 120/60

Apyrexial

Clubbed

Bilateral fine crackles

Investigations:

Hb 13 WCC 13 N 9.0

U+E, LFT normal

CRP 50

Sputum MCS requested

ABG pH 7.45 pCO2 5.5 PO2 9.0 Lactate 0.5

Chest x ray:

Diagnosis:

Community acquired pneumonia

Background of IPF

Management:

Oxygen therapy:

FiO2 28% Saturations 94%

Antibiotics: Augmentin and Clarithromicin

Clexane prophylaxis

Question often asked: Do you stop the Pirfenidone?

POLL OPEN

Vote Trigger

1 Yes0%

2 No0%

3 Don’t know0%

24 hours later: Feeling more short of breath RR 30/min

Working hard; using accessory muscles

Vague chest discomfort/tightness/sharp pain centre of chest – worse on breathing in

Oxygen requirements increased to FiO2 60% to maintain Sats 93%

CRP 130 WCC 18

What would you do next?POLL OPEN

Vote Trigger

1 Intubate and ventilate0%

2 Perform CTPA0%

3 Escalate antibiotics to second line0%

4 Perform Echocardiogram0%

5 Perform HRCT0%

6 High flow nasal oxygen0%

Management: High Flow nasal oxygen

FiO2 50%

Escalated antibiotics Tazocin

Additional tests: Urine leigonella and

pneumoccocal antigen

PCR Respiratory viruses

Sputum MCS

Performed HRCT to assess for ground glass (could request HRCT/CTPA if PE in differential)

Too unwell for bronchoscopy and lavage

Need more clinical information:

Known IPF –

What is baseline disease severity – FVC 65% DLCO 45%

Baseline exercise tolerance 100-200yards; Progressive decline over 12months Previously 500 yards a year ago

Differential Diagnosis in patients with Acute Worsening of ILD.

Heart Failure – Prior history, CxR (kerley B lines, Cardiomegaly, pleural effusions) ECG, ECHO, raised BNP

Pulmonary Embolism – Typical history; normal CxR, Raised D dimer

Pneumothorax – CxR

Infection – History, CxR, Raised inflammatory markers, Positive cultures

Acute Exacerbation of IPF/ILD

Revised Definition of AE-IPF Revised definition:

An acute, clinically significant respiratory deterioration characterised by evidence of new widespread alveolar abnormality

Revised Diagnostic criteria:

Previous or concurrent diagnosis of IPF

Acute worsening or development of dyspnoea typically less than 1 month duration

New ground glass +/- consolidation on CT on background of UIP pattern

Exclude cardiac failure or fluid overload

Unpredictable course

5-10% AE rate per year in clinical trials

As high as 15% in retrospective studies

Frequency increased in more advanced disease

Accountable for 40% of IPF deaths

Risk Factors:

More severe disease Lower FVC DLCO Oxygen use More extensive CT

High BMI

Cardiovascular disease

Pulmonary Hypertension

Winter-Spring months

Potential Triggers:

Infection

Drugs eg chemotherapy 8-30%, biologics, radiotherapy

Aspiration

Post procedural: Lung bx 2-4% Resection up to 30%

Management: High Flow nasal oxygen

Maintain Saturations above 90%

Broad spectrum iv antibiotics

If no improvement after 3 days (my practise – not evidence based) as everything pointing to infection

Start iv methylprednisolone 500mg-1g of for 3 consecutive days to treat AE-IPF (diffuse alveolar damage)

ATS/ERS Majority of patients with acute exacerbation of IPF

should be treated with corticosteroids, but corticosteroids may not be reasonable in the minority (weak recommendation, very low quality evidence)

Uncontrolled studies only: 4: Steroids ; 4: Cyclophosphomide 5: Polymyxin B

What others may do:

Cyclophosphomide : 4 studies

Tacrolimus: Horita et al 2011 Median survival>92daysvs 38days

Rituximab, plasma exchange and iv ImmunoglobulinDonahoe et al 2015 n=11 vs historical n=20 1 yearsurvival 46% vs 0%

Thrombomodulin

Do you stop antifibrotics? Omit if cant maintain oral intake

Ideally continue as shown to prevent AE-IPF

Case 2: 37 year old female

Insurance sales

Non smoker

PMH: Pancreatitis and cholecystectomy 3 years ago

Oct 15 developed Upper resp tract viral infection

Chronic cough and breathlessness ETT 100yards

Associated wheeze

No benefit from inhalers or PPI

Much better after a course of steroids for presumed asthma

May 16

Developed severe breathlessness, cough and fever

CRP 50 WCC 13 N9.0

Treated with oxygen therapy and antibiotics for Community acquired pneumonia

Sep 17:

Not quite right since discharge

Progressive breathlessness and cough for a few month

Muscle aches all over 4 weeks

Fever

Generalised muscle weakness

Examination:

Flushed

P120 BP 120/50

RR 20/min Sats 88% on air

Temp 37.5

Generalised muscle pain

Dry cracked hands

Bibasal reduced air entry and basal creps

Investigations:

Hb 13 WCC 13 N 9.0

U+E, LFT normal

CRP 100

Sputum MCS requested

ABG pH 7.45 pCO2 5.5 PO2 9.0 Lactate 0.5

Chest x ray:

Diagnosis:

Community acquired pneumonia

?Viral

Management:

Oxygen therapy:

FiO2 60% Saturations 94%

Antibiotics: Augmentin and Clarithromicin

Clexane prophylaxis

What would you do next?POLL OPEN

Vote Trigger

1 Start antiviral therapy0%

2 Perform HRCT0%

3 High flow nasal oxygen0%

4 Perform Viral PCR0%

5 Perform CK0%

Additional tests: Urine leigonella and

pneumoccocal antigen

PCR Respiratory viruses

Sputum MCS

CK>1000

Autoimmune screen

Performed HRCT

Awaited

Awaited

Jo-1 positive

HRCT10

Anti-synthetase Syndrome Idiopathic Inflammatory

myopathies

Antibodies to tRNAacetylating enzymes

Jo1; PL7; EJ; OJ; KS

ILD>60% often predates systemic symptoms

60-85%% survival

Myositis elevated CK

Relatively acute onset disease

Constitutional symptoms

Reynauds

Mechanical hands

Inflammatory polyarthropathy

Can have DM skin lesions

Treatment: Prednisolone 0.5(-1mg)/kg taper dependent on

response

If acute high dose 1mg/kg or Methylprednisolone 1g od for 3 days

Second line: Cyclophosphomide IV vs Rituximab

Rituximab for anti-synthetase syndrome- ILD

Norwegian Retrospective case series n=11

Severe and progressive ILD

Failed Cycloph

Ritux stabilised or improved lung function in 7/11 over 6 months

Well tolerated

1 fatal infection

Retrospective

N=50 (33 CTD; 6 HSP; 11 Other)

Severe disease baseline FVC 44% DLCO 24.5%

Unresponsive to conventional Rx

6% improvement in FVC; stabilisation of DLCO

4% serious infection

Do you escalate to ICU? Not all ILD is IPF

IPF 30% of all ILDs

How convert complicated nomenclature to predicting prognosis hence support

decision making for ICU

INFLAMMATION.REVERSIBLETREATABLEBETTER PROGNOSIS

FIBROSIS.IRREVERSIBLEPOOR TREATMENTPOORER PROGNOSIS

CTD NSIPSSc NSIPDM/PM

HSP - Acute

Drug Toxicity

SarcoidStage 1,2,3

AIP

COP

EO Pneum

DIP/RB-ILD

IPF Fibrotic NSIP

Stage 4 Sarcoid

CTD – UIPRA

CONSIDER ICU ADMISSIONREVERSIBLETREATABLEBETTER PROGNOSISIF COMORBITIES ALLOWCASE BY CASE BASISPATIENT FACTORS

RISK ASSESSMENT vsPROGNOSISIRREVERSIBLEPOOR TREATMENTPOORER PROGNOSISCOMORBIDITIES

INFLAMMATION.REVERSIBLETREATABLEBETTER PROGNOSIS

FIBROSIS.IRREVERSIBLEPOOR TREATMENTPOORER PROGNOSIS

Ground Glass Traction Bronchiectasis

Architectural Distortion

FibrosisHoney Combing

Risk Assessment in Fibrotic Lung Disease

No validated prognostic system

Prognosis is dependent on the type of Interstitial Lung

Disease

Staging: No ideal score Age

Dyspnoea scale

FVC

DLCO

Desaturation during 6MWT

Extent of fibrosis on HRCT

PH

What is the extent of irreversibility? – Fibrosis

Fibrosis/Traction bronchiectasis/UIP

Difficult to quantify – Automated CALIPER

Different patterns: UIP worse than NSIP

Severity of Lung Function – Low FVC Low DLCO at baseline

What is the prior history? Prior history of decline FVC decline >10% DLCO>15%

Age

Impact of Comorbidities in ILD on Risk of death

Are there any models in ILD? YES for IPF;

Risk Assessment in Fibrotic Lung Disease.

Conclusion: Wide differential in acute deterioration of ILD including

infection, PE or acute exacerbation

Consider treating acute exacerbation of ILD with methylprednisolone

I+V not recommended for IPF but consider for all non-IPF