Ppt on interstitial lung disease based on latest ATS guidelines and images from standard radiology book.

1. Approach to diagnosis of
Interstitial lung disease
Dr.Emil Mohan moderator: Dr. Neeraj Gupta sir

2. Introduction
• Interstitial lung diseases (ILDs) are a broad and heterogeneous group
of lung diseases with overlapping clinical, radiological, and
histopathological features
• These disorders are sometimes called diffuse parenchymal lung
disease to make that interstitium is not only compartment of the lung
affected.

3. Classification of interstitial lung disease on the basis of known or unknown etiology
Source: Harrison’s textbook of internal medicine,20 th edition

4. Etiopathogenesis

5. Clinical features
• Typical presentation-Non specific
• Vague symptoms –dyspnea on exertion, cough and an abnormal radiograph
• Acute forms of ILD must be distinguished from resp infections and pul
edema due to CHF
• Immunocompetant patients present as lack of response to antibiotics
• Wheezing –airway centered process i.e HSP,eosinophilic pneumonia or
sarcoidosis
• Substernal chest pain-sarcoidosis
• Pleuritic chest pain-CTD,pneumothorax in LCH
• Hemoptysis- diffuse alveolar haemorrhage

6. Systemic symptoms
• Skin-heliotropic rash,gottron’s papules ,skin tightness,raynaud’s
phenomenon-dermatomyositis
• Papular eruptions ,lupus pernio,erythema nodosum-sarcoidosis
• Malar rash,photosensitivity,skin reaction,hair loss- SLE
• GI symptoms-esophageal motility problem(systemic
sclerosis/polymyositis)
• Bloating,diarrhea-IBD or bacterial overgrowth due to bowel
dysmotility in systemic sclerosis

7. Muskuloskeletal complaints-
• Arthalgia,morning stiffness,joint swelling,erythema and deformities-
RA,Sjogren’s syn,Mixed connective tissue disorders
• Swollen fingers(sausage digits)-SSc,polymyositis
• Raynaud’s phenomenon,digital ulcerations or gangrene-
scleroderma,MCTD,SLE, anti-synthetase syndrome
• Ophthalmologic symptoms-dry eyes or use of eye drops(Sjogren syn
or overlap connective tissue disorders)
• H/o uveitis-sarcoidosis
• Neurologic symptoms -vasculitis, sarcoidosis

8. Cardiac symptoms
• Increasing edema, syncope, exertional chest discomfort-PH/cor-
pulmonale
• Pul arterial hypertension-systemic sclerosis
• Palpitaions/syncope-cardiac sarcoidosis
• Pleuritic chest pain,leg swelling, increasing dyspnea-pul. Embolism

9. Past medical history
• HIV-lymphocytic interstitial pneumonia,(LIP)
• CKD-vasculitis, pulmonary –renal syndromes, or connective tissue
disorder
• Liver disease –sarcoidosis, primary biliary cirrhosis,
• Bell’s palsy-sarcoidosis

10. Occupational history
Occupation Type of ILD EXPOSURE
Stone cutter
Miner
Sand blaster
silicosis Crystalline silica dust
Metal grinder Giant cell interstital pneumonia Cobalt, tungsten
Metal worker berylliosis beryllium
Coal worker CWP Coal dust
Bird breeder Bird breeder’s lung Bird droppings
Bird feathers
Farm
haying Farmer’s lung
Thermophilic bacteria
Fishman’s pul disease and disorders,p 812

12. Update of the classification of idiopathic interstitial pneumonias
Major idiopathic interstitial pneumonias
• Idiopathic pulmonary fibrosis
• Idiopathic nonspecific interstitial pneumonia
• Respiratory bronchiolitis-interstitial lung disease
• Desquamative interstitial pneumonia
• Cryptogenic organising pneumonia
• Acute interstitial pneumonia
Rare idiopathic interstitial pneumonias
• Idiopathic lymphoid interstitial pneumonia
• Idiopathic pleuro-parenchymal fibroelastosis
Unclassifiable idiopathic interstitial pneumonias
Source: OFFICIAL STATEMENT OF THE AMERICAN THORACIC SOCIETY (ATS) AND THE EUROPEAN RESPIRATORY SOCIETY (ERS), MARCH 2013

13. High-resolution computed tomography (CT) images demonstrating a usual interstitial pneumonia
pattern.

14. IDIOPATHIC INTERSTITIAL
PNEUMONIAS

15. Idiopathic pulmonary fibrosis
• IPF is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause.
• Clinically suspected of having IPF” = unexplained symptomatic or asymptomatic patterns of bilateral
pulmonary fibrosis on a chest radiograph or chest computed tomography, bibasilar inspiratory
crackles, and age greater than 60 years.
**IPF is the likely diagnosis when any of the following features are present
• Moderate-to-severe traction bronchiectasis/bronchiolectasis (defined as mild traction
bronchiectasis/bronchiolectasis in four or more lobes including the lingual lobe, or moderate to
severe traction bronchiectasis in two or more lobes) in a man over age 50 years or in a woman over
age 60 years
• Extensive (.30%) reticulation on HRCT and an age 70 years
• Increased neutrophils and/or absence of lymphocytosis in BAL fluid
• Multidisciplinary discussion reaches a confident diagnosis of IPF.
**CLINICAL PRACTICE GUIDELINE OF THE AMERICAN THORACIC SOCIETY (ATS), EUROPEAN
RESPIRATORY SOCIETY (ERS)

16. Pathogenesis
• Basement membrane injury-loss of type 1 pneumocytes
• Alveolar epithelial apoptosis
• Endoplasmic reticulum stress
• Development of myofibroblast and new collagen(epithelial to
mesenchymal transition)
• Growth factors –keratinocyte growth factor,TGF-b,insulin like growth
factor,PDGFTyrosine kinase signalfibroblast proliferation

17. Idiopathic pulmonary fibrosis
• The incidence of IPF increases with older age, with presentation typically consisting of insidious
onset of dyspnea in the sixth and seventh decades .
• Rarely, patients with IPF may present with an acute exacerbation as an initial manifestation
• Patients with IPF who are younger than 50 years old are rare.
• More men have been reported with IPF than women, and the majority of patients have a history of
past cigarette smoking .
• Other risk factors associated with IPF include gastroesophageal reflux , chronic viral infections
such as Epstein- Barr virus , hepatitis C, and a family history of ILD. Many patients with IPF also
have other comorbid conditions that include emphysema (combined pulmonary fibrosis and
emphysema), lungcancer, pulmonary hypertension, sleep apnea, and coronary artery disease.
• In some patients, biological members of the family (primary relatives) also have IPF
• identified genetic factors in the telomerase and telomere pathways are also associated with other
ILDs .

22. D/D
• Asbestosis
• Chronic aspiration
• Radiation pneumonitis
• Chronic hypersensitivity pneumonitis
• End stage sarcoidosis
• Gaucher’s disease
• Niemann-Pick disease
• Hermansky –Pudlak syndrome
• Fibrotic NSIP
• Cryptogenic organizing pneumonia

23. • All symptomatic IPF patients with FVC of >50% predicted should be initiated on pirfenidone
• The patients on pirfenidone developing ≥10% subsequent decline in FVC in any 6–12 months
period should be given a choice of continuation of therapy or switch to an alternative therapy
depending on case to case basis
• All symptomatic IPF patients with FVC of >50% predicted should be initiated on nintedanib
• The patients on nintedanib developing ≥10% subsequent decline in FVC in any 6–12 months
period should be given a choice of continuation of therapy or switch to an alternative therapy
• Either Pirfenidone or Nintedanib may be chosen for patients with IPF based on patient preference
and
tolerability
• Antiacid treatment may be initiated in patients wth IPF at the time of diagnosis

24. • No randomized controlled trials have been conducted with
• corticosteroid monotherapy
• We recommend that patients with IPF
• and clinically significant resting hypoxemia should be
• treated with long-term oxygen therapy (strong recommendation,
• very low-quality evidence).
• We recommend that appropriate patients
• with IPF should undergo lung transplantation (strong
• recommendation, low-quality evidence).

25. Non –specific interstitial pneumonia
• HRCT -bilateral ground-glass opacity, Irregular reticular opacities
with traction bronchiectasis and bronchiolectasis
• Subpleural sparing may be helpful in distinguishing NSIP from UIP
Honeycombing is sparse or absent at presentation
• The histologic features include varying amounts of interstitial inf
lammation and fibrosis with a uniform appearance
• Most cases of NSIP have a predominantly fibrotic pattern(less likely
to resolve with medical therapy) of injury with rare cases of isolated
cellular NSIP(potentially responsive to medical therapy)

27. Smoking related ILD
respiratory bronchiolitis-ILD and desquamative intertitial pneumonia
• RB-ILD and DIP are continuous spectrum of disease primarly affecting tobacco smokers
• Pathologic hallmark-brown pigment in macrophages
• RB-ILD-peribrochial inflammation and fibrosis
• DIP-involves airways but also extend into alveolar spacesand include intertitial fibrosis
• Characteristic HRCT features - groundglass opacity and centrilobular nodules ,Central
brochial wall thickening
• In clinical practice, RB-ILD is increasingly diagnosed without surgical lung biopsy in
smokers with these HRCT findings and where bronchoalveolar lavage demonstrates
smokers’ macrophages and the absence of lymphocytosis
• Histopathology:pigmented macrophages with chronic inflammation
• The disease course is heterogeneous, with a significant minority having progression
despite smoking cessation

28. associations
• RB-ILD And DIP -Tobacco smoke
• DIP-marijuana,diesel fume, beryllium, copper, asbestos
• DIP- RA, and scleroderma, hepatitis C, cytomegalovirus, and
aspergillus
• Abnormality in surfactant function

29. (A)
Axial and (B) coronal computed
tomography (CT)
reconstructions
in a 47-year-old heavy cigarette
smoker show moderately
extensive ground-glass
opacities
and centrilobular nodules
(circles).
The bronchi are markedly
thickwalled
and there is minimal
emphysema.
Bronchoalveolar lavage
yielded 91% macrophages. (C)
Histologic features: lung biopsy
shows peribronchiolar
pigmented
macrophage accumulation and
emphysema. (D) There is mild
bronchiolar fibrosis and
pigmented

30. Treatment-RBILD ,DIP
• Discontinue smoking
• Immunosuppresive drugs-prednisolone 40 to 60 mg/d for 6 weeks
• Lung tranplantation
• No strong evidence that therapies are effective

31. Cryptogenic organizing pneumonia.
• Pathologic hallmark of COP-whorls of myofibroblast and inflammatory cells in a
connective tissue matrix within the distal air spaces –called “organizing
pneumonia”
• Initialy called “bronchiolitis obliterans organizing pneumonia”-changed in 2002
• COP dominates the airspaces and not interstitium
• present with a subacute illness of relatively short duration with variable degrees
of cough and dyspnea
• Small unilateral or bilateral pleural effusion may occur in 10–30% of patients.
• The OP pattern is a patchy process characterized primarily by organizing
pneumonia involving alveolar ducts and alveoli with or without bronchiolar
intraluminal polyps.
• COP continues to be included in the classification of IIP because of its
idiopathic nature

32. • Prodromal flu-like illness and symptoms of fever,cough, and dyspnea
• Auscultation-clear or crackles
• Patient is frequently treated with multiple courses of antibiotics
before diagnosed

33. Associations
• Influenza H1N1
• Drug-nitrofurantoin,phenytoin,amiodarone, cocaine
• Occupatinal exposure-textile dye acramin,titanium nanoparticles in
paint,
• Dermatomyositis-polymysitis,RA, SLE,
• Radiotherapy particularly after breast cancer radiotherapy after 3 to 6
months.
• Tranplant rejection, GVHD,

34. treatment
• 3 month duration of corticosteroids
• Macrolide antibiotics

35. HRCT - patchy and often migratory consolidation in a subpleural, peribronchial, or bandlike pattern with ground-glass opacity
and reversed halo (or atoll) sign.
A)peripheral consolidation
and air bronchograms, (B)
bronchocentric distribution,
(C) perilobular pattern showing
focal right lower lobe consolidation,
with more central
ground-glass opacity,
corresponding
to the reversed
halo sign, and (D) bandlike
consolidation.

36. ACUTE INTERSTIAL PNEUMONIA
• AIP is a distinct IIP characterized by rapidly progressive hypoxemia,
mortality of 50% or more, and no proven treatment.
• HRCT shows bilateral patchy ground-glass opacities, often with
consolidation of the dependent lung . The later, organizing stage of
AIP is associated with distortion of bronchovascular bundles and
traction bronchiectasis.
• Biopsy shows an acute and/or organizing form of diffuse alveolar
damage (DAD) that is indistinguishable from the histologic pattern
found in ARDS
• AIP can progress to a pattern similar to fibrotic NSIP

37. Idiopathic Lymphoid Interstitial Pneumonia
• Most cases of LIP are associated with other conditions, although
idiopathic cases still rarely occur .
• More common in females-age fifth decade
• Most cases of LIP are associated with sjogrn’s syndrome or
immunodeficiency as severe combined immunodeficiency or
HIV,Hashimoto disease,c/c active hepatitis,SLE,autoimmunohemolytic
anemia,primary biliary cirrohis, and hypogammaglobulinemia
• Viral infection-EB,HTLV-1,
• Diffuse, lower lobe predominant GGO and small cysts –HRCT
• Pathology-lymphoid infiltrate with lymphocytes,plasma cells, and
histiocytes with type II cell hyperplasia
• prognosis-50% will improve,10% remain stable and 40% will die of
disease.

38. • Diffuse, patchy or lower lobe predominant GGO + Reticular markings
and small cysts.difficult to distinguish from viral, or PCP or CMV
pneumonia.
• LIP with Sjogren-B/L thin walled cysts of varying sizes(larger than cysts
in AIDS-LIP)
• Vessel appears to be associated with the wall of a cyst-perivascular
cyst
• D/D –other cystic lung disease-LAM,LCH,PCP (latter upper lobe
predominat)

39. Idiopathic Pleuro-parenchymal Fibroelastosis
• PPFE is a rare condition that consists of fibrosis involving the pleura
and subpleural lung parenchyma, predominantly in the upper lobes.
• HRCT shows dense subpleural consolidation with traction
bronchiectasis, architectural distortion, and upper lobe volume loss .
• The fibrosis is elastotic, and intra alveolar fibrosis is present
• Pneumothorax is common

40. ILD associated with CTD

41. Systemic sclerosis
• ILD is m/c pulmonary manifestation
• Pulmonary HTN can occur separately or concomitantly with ILD
• Most frequent in limited SSc
• HRCT-NSIP and IPF can be present
• Dilated esophagus and pul artery enlargement

42. Rheumatoid arthritis
• Common extraarticular complication of RA
• RA-ILD more frequent in males
• 10% of RA population
• HRCT-UIP pattern;survival is decreased in UIP pattern
• Histopath-histopathologic findings of UIP and NSIP pattern
• Treatment-immunosuppressive,cytotoxic drugs,antifibrotic
pirfenidone,nintedanib

43. Dermatomyositis/polymyositis
• ILD present in 45% patients positive anti-synthetase Ab
• Anti Jo-1 Ab develop rapidly progressive ILD
• HRCT-NSIP pattern common,rare UIP pattern also seen

44. Langerhans cell histiocytosis
• Granulomatous disease characterised by presence of large histiocytes
containing racket shaped organelles
• Majority are cigarrete smokers
• Present with dyspnea,cough or pneumothorax
• HRCT:reticulonodular shadowing in the mid and upper zonesthat are
of normal or increased volume
• Nodules further cavitate to a combination of cysts and nodules which
spare costophrenic recesses even in advanced disease

45. lymphangioleiomyomatosis
• Histologically two feature:cysts and proliferation of atypical smooth
muscle cells of pulmonary interstituim in bronchioles and lymphatics
• Exclusively in women
• LAM can occur as part of tuberous sclerosis complex
• Present as pleural effusion(chylous) and pneumothorax.
• Pattern of symmetrical reticular or reticulonodular opacities with
normal or increased lung volumes
• Features distinguishing LAM from LCH are diffuse distribution of cysts
with no sparing of bases, more regularly shaped cysts and normal
intervening lung parenchyma

46. Work up
• Complete blood count
• liver and kidney function tests and serum electrolytes
• Chest radiograph and HRCT chest
• Electrocardiogram.
• Pulse oximetry
• Arterial blood gases (if SpO2 < 90%)
• connective tissue disease markers-rheumatoid factor, antinuclear antibody (ANA),myositis panel,
anticyclic citrullinated peptide
• Tr a n s t h o r a c i c e c h o c a r d i o g r a m , c a r d i a c enzymes
• CT pulmonary angiography (only if acute worsening)
• BAL can be considered to rule out infection only if clinically indicated

47. The role of lung function tests in the evaluation of patients with interstitial lung disease

48. LABORATORY TEST
• BAL may be used to diagnose certain rare ILDs such as pulmonary alveolar proteinosis (PAP), PLCH,
and eosinophilic pneumonia .
• When performed, infection must be ruled out (especially Mycobacterium tuberculosis) by special stains,
molecular techniques, and cultures of the BAL specimen, if suspected by the clinician
• Noninvasive tests such as sputum for microbiologic and molecular testing should precede a flexible
bronchoscopy; a positive result obviates the need of a BAL.
• BAL allows sampling of protein and cellular components of the lung fluid.
• BAL fluid appearance itself is diagnostic –bloody lavage in diffuse alveolar hemorrage,milky white or tan
BAL containing debris that settle out s/o pul alveolar proteinosis
• Periodic acid-Schiff stain confirms diagnosis

49. Lung biopsy
1. Conventional TBLB should not be done in patients with UIP pattern on HRCT
2. TBLB may be considered in those patients likely to have ILDs, particularly if the disease has a
tendency for bronchocentric involvement such as sarcoidosis and HP .
3. The site of biopsy site should be guided by HRCT
4. VATS lung biopsy should be preferred over open lung biopsy
5. SLB should not be performed in patients with respiratory failure/those on mechanical ventilation as
it is associated with risk of high mortality

50. CT Protocol recommended
1. Noncontrast examination
2.Volumetric acquisition with selection of
• Submillimetric collimation
• Tube potential and tube current appropriate to patient size
3 Reconstruction of thin-section CT images (91.5 mm):
4 Number of acquisitions
• Supine: Inspiratory (volumetric)
• Supine: Expiratory (can be volumetric or sequential)*
• Prone: Only inspiratory scans
5 Recommended radiation dose for the inspiratory volumetric acquisition
1-3 mSv (i.e., “reduced” dose)

51. Serologic testing in ILD
Test Disease
ANA Scleroderma,SLE,MCTD
SSA Sjogren syndrome
SSB Sjogren syndrome
CK
Jo-1
Myositis asso. Ab
Polymyositis,dermatomyositis
Jo-1
Myositis associated antibody
Antisynthetase syndrome
Scl-70
Anti-centromere Ab
Scleroderma
RF
CCP
Rheumatoid arthritis
RNP
Anti-histone Ab
Mixed connective tissue diseae
P-ANCA,c-ANCA ANCA –asso. vasculitis

52. Lung transplantation
• Potential life extending alternative for fibrotic lung disease
• DLCO<39% and advanced fibrosis on HRCT considered for active listing
• Criteria for considering IPF patients for transplantation include severe dyspnea,
forced vital capacity less than 50% of predicted, resting arterial hypoxemia or
hypercapnia, and pulmonary hypertension

54. TABLE 107-5 Indications for Lung Transplant Procedures
Single-lung transplantation
• Obstructive lung disease
• Restrictive lung disease
• Idiopathic pulmonary arterial hypertension (rarely)
• Eisenmenger syndrome with a correctable shunt defect (rarely)
Bilateral-lung transplantation
• Obstructive lung disease (patient <60 y old)
• Septic lung disease
• Idiopathic pulmonary arterial hypertension
• Eisenmenger syndrome with a correctable shunt defect
Combined heart–lung transplantation
• Significant intrinsic left ventricular dysfunction (LVEF <45%)
• Significant coronary artery disease, not amenable to nonsurgical interventions
• Eisenmenger syndrome with an irreparable shunt defect

55. complications
• Most common comorbidities encountered in ILD are gastroesophageal reflux disease (GERD),
pulmonary hypertension (PH), lung cancer, obstructive sleep apnea (OSA), and venous
thromboembolism (VTE)
• Screening tools for monitoring comorbidities in ILD
• GERD:
• PH: Echocardiography as a screening tool for PH/PAH in ILD patients .
• 3. CT for Lung cancerhistory , chest pain , hemoptysis , and areas of emphysema on HRCT act as
warning signs for lung cancer and should trigger a search for the same.
• 4. OSA: ILD patients with high body mass index (BMI) and a positive sleep apnea screening
questionnaire may be evaluated by polysomnography
• 5. VTE: Sudden onset and/or rapid worsening of dyspnea, palpitations, lower extremity edema

56. Thank you