1. Interstitial Lung Disease
Anne McKay
Consultant Respiratory Physician
Queen Elizabeth University Hospital
Glasgow

2. Outline Classification of ILD Clinical Presentation of ILD
Symptoms
Examination
Initial investigations - X-rays, lung function, bloods
Discuss common types of ILD
Idiopathic pulmonary fibrosis
Sarcoidosis
Hypersensitivity pneumonitis

3. Classification of ILD

4. ATS Classification of Diffuse Parenchymal Lung Disease
Infiltrative processes which involve the alveolar spaces or lung interstitium

5. Pragmatic Classification of ILD
Commonest ILDs - idiopathic pulmonary fibrosis and sarcoidosis
Adapted from Gulati. Prim Care Resp J 2011; 20 (2) 120

6. Initial Presentation and Investigation

7. Clinical Features of ILD
Symptoms
Cough
Breathlessness – acute or chronic
Fatigue
Clinical Signs
Crackles/creptitations in chest
Finger clubbing
Cyanosis
Peripheral oedema

8. Initial Investigation

9. Initial Investigations
CXR – bilateral interstitial changes

10. Initial Investigations
Lung Function Tests
Restrictive defect
FEV1 to FVC ratio normal to high (both values reduced)
CO gas transfer reduced
Pred
Actual
% Pred
FVC (l)
2.80
1.17 42
FEV1 (i)
2.39
1.04 44
FEV1/FVC (%) 80 89 -
TLC (l)
4.57
1.75 38
DLCO (ml/mmHg/min)
23.3 6 26

11. Subsequent Investigations
High Resolution CT chest (HRCT)
Screening blood tests – any underlying cause
Immunology screen – RF, ANA, ANCA
Avian and aspergillus precipitans
Serum angiotensin converting enzyme (ACE) level
Arterial Blood Gases - Type 1 Respiratory Failure
VATS lung biopsy
Six minute walk test/ambulatory oxygen assessment
Echocardiogram

12. Idiopathic Pulmonary Fibrosis (IPF)

13. Idiopathic Pulmonary Fibrosis
Definition:
a specific form of chronic fibrosing interstitial pneumonia of unknown aetiology
limited to the lung
histopathological appearance of usual interstitial pneumonia (UIP) on surgical lung biopsy
other causes excluded (drugs, CTD)
Characteristic radiological and lung function features
(American Thoracic Society/European Respiratory Society, 2009)

14. Clinical Features of IPF
Age of onset > 50,
male > female
Progressive breathlessness, productive cough, cyanosis
Respiratory failure, cor pulmonale, pulmonary hypertension
Fine bilateral end-inspiratory crackles
Finger clubbing (2/3)
usually a h/o cigarette smoking

15. Radiological Changes in IPF
Predominantly at lung bases

16. CXR – irregular reticulonodular changes / honeycombing

17. High resolution CT Chest
Early
Advanced
High resolution CT Chest
subpleural reticular changes
honeycombing
traction bronchiectasis

18. Pathogenesis of IPF
"repeated cycles" of epithelial activation/injury by some unidentified agent
abnormal activation of epithelial cells lead to a dysregulated repair process
inflammatory pathways also promote fibrosis
induction of a Th2 type T cell response
TGF-1β
Abnormal epithelial repair at site of injury/inflammation leads to the formation of the fibroblastic foci

19. UIP Cobblestone surface of lung Fibroblastic foci and temporal
Heterogeneity on histology
Fibroblastic foci
Normal lung
Honeycomb Cysts

20. Treatment of IPF Anti-fibrotic agents - pirfenidone and nintedanib
Approved for use in patients with FVC 50 – 80% predicted
For many, therapy is mainly aimed at symptom control
oxygen, diuretics, antibiotics, pulmonary rehabilitation
Lung transplant for a few (age < 65)

21. Pirfenidone mechanism of action unclear ? suppresses fibroblast growth
slows lung function decline
mechanism of action unclear
? suppresses fibroblast growth
Optimal dose 801 mg tds
Side effects
GI upset
Photosensitivity
ASCEND trial - King TE Jr et al, NEJM 2014; 370:2083

22. Nintedanib intracellular inhibitor of multiple tyrosine kinases
Slows lung function decline (INPULSIS-1 and 2)
Usual dose 150 mg bd
Main side effect is GI upset especially diarrhoea
Richeldi L et al, NEJM 2014; 370: 2071

23. Prognosis in IPF Median survival is 3 – 5 years from time of diagnosis
75% will die from respiratory illness
1 in 10 patients develop lung cancer
Brett L, et al. AJCCM 2011, 183,

24. SARCOIDOSIS

25. Sarcoidosis Multi-system granulomatous disorder Unknown aetiology
Non-caseating granulomas
Unknown aetiology
Commonly affects young adults
Epidemiology
UK prevalence /100,000
Peak incidence in 20s and 30s
F > M

26. Sarcoidosis Antigen SARCOIDOSIS Genetic Factors Disordered Immune
Regulation
Genetic
Factors
Antigen
SARCOIDOSIS

27. Other Factors Genetic factors Environmental factors
Familial and racial clustering
Associated with HLA-A1, HLA-B8
Environmental factors
Mycobacteria
Proprionobacterium acnes
Fungi and viruses
15 times more common in Afro caribbeans, EBV, environmental agents

28. Clinical presentation
Respiratory symptoms
Abnormalities on CXR
Fatigue and weight loss
Peripheral lymphadenopathy
Fever
Skin and eye involvement
Neurological symptoms

29. CXR – Bilateral HilarLymphadenopathy
Erythema Nodosum
CXR – Bilateral HilarLymphadenopathy
EN ImageJamesHeilman, MD, Wikimedia Commons

30. Sarcoidosis - Diagnosis
CXR – bilateral hilar lymphadenopathy, lung infiltrates
CT chest (HR):
nodular changes – subpleural or along bronchovascular bundles
Lung Function Tests
Normal
Airflow obstruction
Restrictive defect
BHL and parenchymal sarcoidosis may be asymtpomatic
Others have progressive breathlessness

31. Sarcoidosis - Diagnosis 2
Tissue Diagnosis
Bronchoscopy → Transbronchial Lung Biopsy
90 % positive if chest disease
Biopsy Mediastinal Lymph Nodes - EBUS
Differential Diagnosis: Lymphoma, TB, Lung Cancer
Blood Tests
FBC – mild anaemia, raised ESR
Serum biochemistry
Hypercalcaemia
Raised gammaglobulins
Serum ACE
TBLB - 50 % positive if extrapulmonary disease , NCNC anaemia, Raised Ca – mention Vit D

32. Respiratory Staging 0 – normal
1 – Bilateral hilar lymph (BHL) nodes alone
2 – BHL with pulmonary infiltrates
3 – Pulmonary infiltrates alone
4 – fibrosis
Small proportion of patients progress to Stage 4
Stage 1 – 3 can be asymptomatic
Some have progressive breathlessness
Stage 1 2/3, Stage 2 ~ 25%, Stage 3 - rest

33. Stage 4 Sarcoidosis – Fibrotic Changes

34. Treatment Most patients do not require treatment
Corticosteroids – if not improving or declining after 6 months
30 mg daily for weeks then taper to 5 – 10 mg daily for a total of 12 months
Methotrexate or azathioprine are common second-line drugs
Mandatory treatment – eye, CNS, cardiac involvement or persistent hypercalcaemia

35. Prognosis Generally sarcoidosis has a very good prognosis
Remittance within 2 years:
Stage 1 – 66 %
Stage 2 – 50 %
Stage 3 – 33 %
Less than 5 % of UK patients progress to respiratory failure and cor pulmonale
High mortality in black americans upto 10 %

36. Hypersensitivity Pneumonitis

37. Hypersensitivity Pneumonitis
Previously called extrinsic allergic alveolitis
Hypersensitivity reaction to inhaled organic dust
Commonest causes in UK:
Farmer’s lung – Micropolyspora faeni
Pigeon fancier’s lung – bloom/excreta
25% of cases no antigen identified

38. HP Clinical Features Acute illness: Examination –
3 – 9 hours after exposure
Malaise, fever, anorexia, fatigue, headache
Dry cough, breathless, wheeze
Examination –
increased respiratory rate and hypoxaemia
bibasal crackles
Chronically – progressive breathlessness, reduced exercise tolerance, weight loss

39. CXR in Acute Hypersensitivity Pneumonitis

40. HRCT Chest in Acute Hypersensitivity Pneumonitis
Case courtesy of Dr Mark Holland , Radiopaedia.org, rID: 19551

41. Pathophysiology Acute non-specific diffuse pneumonitis
Lymphocytic alveolitis – airway/aveolar oedema
Non-caseating granulomata
Circulating antibodies (IgG) to responsible antigen

42. Diagnosis Periodic or continuous exposure to a relevant antigen
Appropriate changes in lung physiology and pathology
Evidence of immunologic sensitisation to the suspected provoking agent

43. Treatment Withdrawal from causal agent Anti-inflammatory agents
“short” courses of oral steroids
Oxygen therapy
Avoidance of further exposure

44. General Management of ILD
Glasgow had an ILD MDT monthly
Attended by Respiratory Consultants, ILD Clinical Nurse Specialist, Radiologist, Pathologist
Discuss difficult cases and review cases where anti-fibrotic therapy might be appropriate

45. Summary
The commonest interstitial lung diseases are idiopathic pulmonary fibrosis and sarcoidosis
Pirfenidone and nintedanib are now available for the treatment of IPF.
ILDs which respond to immunosuppressive treatment generally have a better prognosis
An ILD MDT is helpful in the diagnosis and management of difficult cases

46. Any Questions?