This document provides information on interstitial lung disease (ILD), including its classification, pathogenesis, genetics, clinical presentation, investigations, radiology findings, and treatment approaches. ILD refers to a group of diffuse infiltrative lung disorders characterized by inflammation and scarring of the lung tissues between the air sacs. Specific forms of ILD can be differentiated based on clinical, radiologic, and pathologic findings. Treatment depends on the underlying cause but may include corticosteroids, immunosuppressants, antifibrotic drugs, and lung transplantation in advanced cases.

1. INTERSTITIAL LUNG DISEASE
DR. RUPAN BHADURY
DRNB (CCM) PDT,
MEDICA SUPERSPECIALTY HOSPITAL,KOLKATA

3. • THESE DIFFUSE INFILTRATIVE LUNG DISORDERS ARE TYPICALLY CHARACTERIZED
BY THE PRESENCE OF INFLAMMATION AND ALTERED LUNG INTERSTITIUM, AND
SPECIFIC FORMS OF ILD CAN BE DIFFERENTIATED FROM ONE ANOTHER WHEN
CLINICAL DATA, RADIOLOGIC IMAGING, AND PATHOLOGIC FINDINGS (IF LUNG
BIOPSY IS NEEDED) ARE COMBINED TO REACH A CONFIDENT DIAGNOSIS .
• THE HISTOPATHOLOGIC CHANGES IN THE LUNGS OF PATIENTS WITH ILD CAN
RANGE FROM GRANULOMATOUS INFLAMMATION WITHOUT PARENCHYMAL
FIBROSIS IN PATIENTS WITH SARCOIDOSIS TO EXTENSIVE PULMONARY FIBROSIS
WITH ARCHITECTURAL DISTORTION OF THE LUNG IN PATIENTS WITH IDIOPATHIC
PULMONARY FIBROSIS (IPF).

4. CLASSIFICATION OF ILD

5. PATHOGENESIS OF ILD

6. GENETICS
• MUC5B PROMOTER VARIANT
• GENES INVOLVED IN TELOMERE
LENGTH REGULATION LIKE
• TERT
• TERC
• RTEL1
• SURFACTANT PROTEIN
GENES(SFTPA2)
• TUBEROUS SCLEROSIS COMPLEX
GENES (TSC1 & TSC2)
• HERMANSKY PUDLAK SYNDROME
ASSOCIATED WITH
OCULOCUTANEOUS ALBINISM
,BLEEDING DIATHESIS ,HORIZONTAL
NYSTAGMUS AND GENES LIKE HSP 1
,HSP 7

8. • CLINICAL PRESENTATION-
1) EXERTIONAL DYSPNOEA & DRY COUGH
2) LATE INSPIRATORY CRACKLES
(VELCO CRACKLES).
1) CHEST X-RAY-
SEPTAL THICKENNING &
RETICULONODULAR CHANGES.
4) WHEEZING- HP,SARCOIDOSIS.
5) PLURITIC CHEST PAIN –CONNECTIVE
TISSUE DISORDER.
6) HAEMOPTASIS-
DAH,VASCULITIS,PULMONARY EMBOLISM.

9. APPROACH TO A PATIENT WITH ILD

10. INVESTIGATION

11. ILD RADIOLOGY

12. IPF RADIOLOGY

13. Subpleural
basal
predominance
Reticular
opacities
Honey
combing
pattern

14. GGO
Reticular
opacities
Traction
bronchiecyasis

15. Diffuse GGO
Consolidation

16. Perilymphatic nodules

17. Reverse halo sign(
alveolar septal
inflammation
corresponding to
central GGO and
granulomatous
tissues in peripheral
airspace’s

18. Presence of
centrilobular nodules
Mostly involving
upper lobes

19. USUAL INTERSTITIAL PNEUMONIA
• CHARACTERISED BY PATCHY LUNG FIBROSIS & HONEYCOMBING.
• CAUSES-
1) IDIOPATHIC PULMONARY FIBROSIS (2/3 RD CASES)
2) COLLAGEN VASCULAR DISEASE ( RA & SCLERODERMA).
3) DRUG RELATED FIBROSIS.
4) ASBESTOSIS
5) END-STAGE HYPERSENSITIVITY PNEUMONITIS(HP).

20. KEY DEFINITIONS SEEN IN PATIENTS WITH IPF
• 1) RETICULAR PATTERN:
RETICULAR PATTERN, ALSO SOMETIMES REFERRED TO AS
RETICULATION, CONSISTS OF A FINE NETWORK OR MESH OF
OVERLAPPING LINEAR LINES WITHIN THE SECONDARY PULMONARY
LOBULE.
THIS FINDING SUGGESTS AN INJURY TO THE INTERSTITIUM AND IS
AN INDICATOR OF FIBROTIC ILD IN MANY CASES.

21. • 2) ARCHITECTURAL DISTORTION:
IN THE SETTING OF ILD, THIS GENERALLY REFERS TO AN ABNORMAL
APPEARANCE OF THE SECONDARY PULMONARY LOBULE SHAPE OR
SIZE WITH EVIDENCE OF VOLUME LOSS.
• 3) TRACTION BRONCHIECTASIS AND BRONCHIOLECTASIS:
TRACTION BRONCHIECTASIS AND BRONCHIOLECTASIS BOTH
REFER TO IRREVERSIBLE DILATATION OF AN AIRWAY RELATED TO
SURROUNDING OR ADJACENT LUNG FIBROSIS. THE DILATED AIRWAY
IS OFTEN IRREGULAR AND TORTUOUS.

22. • 4) HONEYCOMB CYSTS:
HONEYCOMB CYSTS ARE SUBPLEURAL CLUSTERED CYSTIC AIR SPACES . THESE
ARE GENERALLY SMALL IN SIZE (3–5 MM). TO BE CONSIDERED AS TRUE
HONEYCOMBING, THE CYSTS MUST BE CONTIGUOUS, AND MUST TOUCH THE
PLEURAL SURFACE.

23. • 5) BASAL PREDOMINANT:
BASAL PREDOMINANT REFERS TO THE DISTRIBUTION OF FINDINGS IN THE
CRANIOCAUDAL PLANE (SUPERIOR TO INFERIOR) BEING MORE LOWER LUNG–
PREDOMINANT. THIS IS THE MOST COMMON PATTERN OBSERVED IN IPF.

25. KEY DEFINITIONS SEEN IN PATIENTS WITHOUT
IPF
• 1) GROUND-GLASS OPACITY:
GROUND-GLASS OPACITY REFERS TO A HOMOGENEOUS AREA OF INCREASED
LUNG OPACITY (A PROCESS WHICH PARTIALLY FILLS THE AIRSPACES) IN WHICH THE
INCREASED OPACITY DOES NOT OBSCURE THE UNDERLYING BRONCHIAL AND
VASCULAR STRUCTURES.
ACUTE- PCP,VIRAL PNEUMONIA,ALVEOLAR HAEMORRHAGE,
ACUTE HP.
CHRONIC (H/O 4-6 WKS)- NSIP,DIP,
ORGANISING
PNEUMONIA.

26. • 2) CONSOLIDATION:
CONSOLIDATION REFERS TO AN AREA OF INCREASED LUNG OPACITY (A
PROCESS WHICH COMPLETELY FILLS THE AIRSPACES) IN WHICH THE INCREASED
OPACITY DOES OBSCURE THE UNDERLYING VASCULAR AND BRONCHIAL
STRUCTURES.
3) MOSAIC ATTENUATION & AIR TRAPPING

28. NSIP RADIOLOGY
• 1) PREDOMINANCE IN
PERIPHERAL,BASAL,POSTERIOR LUNG
REGIONS.
• 2) SPARING OF IMMEDIATE SUBPLEURAL
REGION (MOST SIGNIFICANT SIGN).
• 3) GGO IN CELLULAR NSIP.
• 4) RETICULATION & TRACTION
BRONCHIECTASIS.
• 5) RARELY HONEYCOMBING.
• 6) FEATURES OF VOLUME LOSS.

30. ACUTE EXACERBATION OF ILD

31. • THE CLINICAL PRESENTATION OF AE-ILD IS USUALLY A RAPID WORSENING OF
RESPIRATORY SYMPTOMS WITH INCREASED DYSPNEA WITHIN LESS THAN
1 MONTH
• ADDITIONAL FINDINGS CAN BE COUGH, INCREASED SPUTUM PRODUCTION,
FEVER, AND FLU-LIKE SYMPTOMS .
• ESTABLISHED CRITERIA FOR A PRESENTING ABNORMAL GAS EXCHANGE IS A
PAO2/FIO2 < 250 OR PAO2 DECREASED> 10 % OVER TIME OR
FVC & DLCO DECREASED > 10% FROM PREVIOUS VALUE.

33. CAUSES OF AE - IPF
1) INFECTION-
THERE IS AN INCREASING NUMBER OF FINDINGS INDICATING THAT
INFECTION, BOTH VIRAL AND BACTERIAL, MIGHT BE INVOLVED IN
SOME CASES OF AE-ILD.
PATIENTS WITH AE-IPF EXPERIENCED A MARKABLE CHANGE IN THE
RESPIRATORY MICROBIOME WITH AN INCREASE IN CAMPYLOBACTER
SP. AND STENOTROPHOMONAS SP.
2) MICROASPIRATION-
PATIENTS WITH AE-IPF HAD SIGNIFICANTLY HIGHER LEVELS OF
PEPSIN IN BAL COMPARED TO STABLE CONTROLS, SUGGESTING AN
INVOLVEMENT OF OCCULT ASPIRATION.
3) PULMONARY EMBOLISM

34. DIAGNOSIS
• 1) RADIOLOGY –
BILATERAL GROUND-GLASS OPACITY AND/OR CONSOLIDATION
ON A BACKGROUND OF USUAL INTERSTITIAL PNEUMONIA (UIP)
PATTERN IS SUFFICIENT TO CONFIRM THE RADIOGRAPHIC
DIAGNOSTIC CRITERIA OF AE-IPF . THE TERM “SUSPECTED AE-IPF”
SHOULD BE USED IF THERE ARE ONLY UNILATERAL GROUND GLASS

35. • 2) BLOOD TEST-
INCREASED WHITE BLOOD CELL COUNT, ELEVATED VALUES OF ERYTHROCYTE
SEDIMENTATION RATE, AND C-REACTIVE PROTEIN AND INCREASED LACTATE
DEHYDROGENASE .
• 3) BAL STUDY-
AE-IPF AND AE-HP ARE ASSOCIATED WITH AN INCREASE IN NEUTROPHILS IN BAL
.
THE RIGHT MIDDLE LOBE OR LINGULA OF THE LEFT UPPER LOBE ARE LIKELY THE
BEST REGIONS TO PERFORM LAVAGE WHEN DIFFUSE DISEASE IS PRESENT, AND
AREAS WITH GROUND GLASS OPACIFICATION OR PROFUSE NODULAR CHANGE ARE
MORE LIKELY TO PROVIDE USEFUL DIAGNOSTIC INFORMATION.

36. TREATMENT IN AE-ILD
• ACUTE EXACERBATIONS OF INTERSTITIAL LUNG DISEASE IS A LIFE THREATENING
EVENT AND THE MORTALITY RATE IS HIGH.
• IT IS ASSUMED THAT BETWEEN 35 AND 46% OF DEATHS IN IPF ARE CAUSED BY
AE-IPF.
• POOR PROGNOSTIC FACTOR-
1) LOWER BASELINE PULMONARY FUNCTION PARAMETERS (FVC AND
DLCO).
2) HIGHER FIBROSIS SCORE OR MORE EXTENSIVE DISEASE ON HRCT.
3) A PREVIOUS AE-IPF.
4) YOUNGER AGE – AE-IPF & OLDER AGE – AE-CTD –ILD.
5) PULMONARY HYPERTENSION,ISCHEAMIC HEART DISEASE .
BASED ON AN ESTIMATED 90% IN-HOSPITAL MORTALITY, THE
INTERNATIONAL GUIDELINES ON THE MANAGEMENT OF IPF MAKE A

38. STEROID THERAPY IN AE- ILD

39. PULE DOSE OF
METHYLPREDNISOLNE(1GM/DAY/3DAY)

40. INDICATIONS OF GLUCOCORTICOID THERAPY IN ILD
• 1)EOSINOPHILIC PNUEMONIA
• 2) COP
• 3)CTD-ILD
• 4) SARCOIDOSIS
• 5) HYPERSENSITIVITY PNEUMONITIS(ACUTE & CHRONIC)
• 6) ACUTE RADIATION PNEUMONITIS
• 7) DIFFUSE ALVEOLAR HAEMORRHAGE

41. • HIGH-DOSE STEROID MONOTHERAPY (0.5–1
MG/KG) DOES NOT IMPROVE SURVIVAL OR
OTHERWISE MODIFY THE CLINICAL COURSE OF THE
DISEASE AND IS ASSOCIATED WITH SIGNIFICANT
MORBIDITY. IT IS THEREFORE STRONGLY
RECOMMENDED THAT HIGH-DOSE STEROIDS NOT
BE USED TO TREAT PATIENTS WITH IPF.
• REFERRAL TO A TRANSPLANT CENTRE
SHOULD BE MADE IF THE DISEASE IS
ADVANCED (TLCO ,40% PREDICTED)
OR PROGRESSIVE (>10% DECLINE IN
FVC OR >15% DECLINE IN FVC DURING
6 MONTHS OF FOLLOW-UP).
• FOR THE MAJORITY OF CTD, WITH THE EXCEPTION
OF SYSTEMIC SCLEROSIS (SSC), RECOMMENDED
INITIAL TREATMENT FOR ILD IS ORAL
PREDNISOLONE AT AN INITIAL DOSE OF 0.5–1
MG/KG WITH THE AIM OF TAPERING TO A
MAINTENANCE DOSE OF 10 MG/DAY OR LESS,
OFTEN IN ASSOCIATION WITH AN
IMMUNOSUPPRESSIVE AGENT (USUALLY ORAL OR
INTRAVENOUS CYCLOPHOSPHAMIDE OR ORAL
AZATHIOPRINE).
• IN SSC-ASSOCIATED ILD,
RECOMMENDED TREATMENT, IF
REQUIRED, IS WITH LOW-DOSE
ORAL STEROIDS (10 MG/DAY)
AND/OR CYCLOPHOSPHAMIDE
(ORAL OR INTRAVENOUS). HIGH-
DOSE CORTICOSTEROID

42. ANTI –FIBRINOLYTIC DRUGS
• 1) PERFINEDONE-
IT IS A TGF –BETA INHIBITOR ,CAUSING INHIBITION OF FIBROBLAST
PROLIFERATION & INHIBITING COLLAGEN DIPOSITION.IT ALSO HAS ANTI-
INFLAMMATORY, ANTI-OXIDATIVE PROPERTY.

43. . Of 275 patients randomised (high-dose,
1,800 mg?day-1; low-dose, 1,200
mg?day-1; or placebo groups in the ratio
2:1:2), 267 patients were evaluated for
the efficacy of pirfenidone.

44. NINTEDANIB

45. OTHER THERAPIES
• 1) OTHER IMMUNOSPPRESANT -
A) METHOTREXATE- METHOTREXATE IS ONE OF THE MOST COMMONLY USED
CORTICOSTEROID-SPARING THERAPIES FOR SARCOIDOSIS.
DOSAGE ADJUSTMENT MAY BE NEEDED OR AN ALTERNATIVE
CORTICOSTEROID-SPARING DRUG MAY BE CONSIDERED IN THOSE WITH
RENAL INSUFFICIENCY, E.G. SERUM CREATININE > 1.5 (GFR < 50 ML/MIN).
B) MMF-
FISHER ET AL SHOWED THAT, IN A LARGE DIVERSE COHORT
OF CTD-ILD, MMF WAS WELL TOLERATED AND HAD A LOW RATE OF
DISCONTINUATION. TREATMENT WITH MMF WAS ASSOCIATED WITH EITHER
STABLE OR IMPROVED PULMONARY PHYSIOLOGY OVER A MEDIAN 2.5 YEARS
OF FOLLOWUP. MMF APPEARS TO BE A PROMISING THERAPY FOR THE
SPECTRUM OF CTD-ILD.
THE PRINCIPAL ADVERSE REACTIONS ASSOCIATED WITH THE

46. • C)CYCLOPHOSPHAMIDE –

48. • D)SILDENAFIL-
MAY BE USED TO TREAT SECONDARY PULMONARY HYPERTENSION,
THERE IS SIGNIFICANT IMPROVEMENT ,BUT 6 MWT RESULT WAS NOT ALTERED (IPF
NET PHASE 3 TRIAL).
• E) ANTI –EFFLUX THERAPY-
LESS FVC DECLINE IN PATIENTS ,WHO HAVE TREATED WITH ACID SUPPRESSION
THERAPY(IPF NET SPONSORED TRIAL).