A BRIEF REVIEW OF THE INTERSTITIAL LUNG DISASESES

1. Overview of ILDs
Mulugeta A. (MD,INTERNIST)
Aprill, 2023
FHCSH

2. Outline
• Introduction
• Classification
• Pathogenesis
• Clinical approach
• Treatment

3. Introduction
• ILDs are a heterogeneous group of disorders that are classified
together because of similar clinical, radiographic, physiologic, or
pathologic manifestations
• Also known as diffuse parenchymal lung diseases (DPLDs)
• “interstitial”- indicates the abnormality begins in the interstitium
– It’s a misleading term as most of these disorders are also associated
with extensive alteration of alveolar and airway architecture
• Are associated with considerable rates of morbidity and mortality,
• little consensus regarding the best management of most of them.

4. Classification
• >200 diseases are known to be associated with diffuse
parenchymal lung involvement making classification of ILDs
very difficult
– Primary conditions, or
– Part of multiorgan process
• There are various classification schemes
1. Based on the major underlying histopathology
a) Those associated with predominant inflammation and fibrosis
b) Those with predominantly granulomatous reactions in
interstitial or vascular areas

7. 2. Based on the cause
a) DPLDs of known cause or association
b) Idiopathic
I. Idiopathic interstitial pneumonias
II. Granulomatous DPLDs
III. Other forms of DPLDs
• The treatment choices and prognosis depend mainly on the causes and
types of ILD, so ascertaining the correct diagnosis is important
• A variety of infections can cause interstitial opacities on CXR, including
– fungal,
– atypical bacterial ,and
– viral pneumonias, especially in immunosuppressed individuals
• R/O these conditions before considering ILD

9. • The most common identifiable causes of ILD are
exposure to occupational and environmental agents,
especially the inhalation of inorganic dusts, organic
dusts, and various fumes or gases
• Sarcoidosis, and idiopathic pulmonary fibrosis (IPF) are
the most common ILDs of unknown etiology.
• ILD can also complicate the course of most of the
connective tissue diseases like
polymyositis/dermatomyositis, rheumatoid arthritis ,
and SLE

11. Pathogenesis
• ILDs are nonmalignant
disorders and are not
caused by identified
infectious agents
• The precise mechanism
leading from injury to
fibrosis is not known
• Although there are multiple
initiating agents, the
mechanisms of repair have
common features leading to
common clinical findings

12. Pathology
• Granulomatous lung disease
– Accumulation of T lymphocytes, macrophages, and epitheloid
cells forming granulomas in the lung parenchyma
– Pts often remain free of severe impairment of lung function
despite having extensive lesions on CXR
– Causes- sarcoidosis and hypersensitivity pneumonitis
• Inflammation and fibrosis
– Histopathologic patterns- UIP, NISP, RB-ILD, DIP, COP, DAD, LIPs
– Lead to irreversible scarring and fibrosis of alveolar walls,
airways, or vasculature resulting in derangement of ventilatory
function and gas exchange

13. Clinical Approach
• Patients with ILD commonly present with
– Symptoms of progressive dyspnea
– Persistent dry cough
– Symptoms associated with the underlying disease, such as CTDs
– History of occupational smoking
– Abnormal chest radiograph
– Restrictive pattern on spirometry
• Certain peculiar features of presentations help to
differentiate the different types of ILDs
– Hemoptysis
– Wheezing
– Pleuritic chest pain

14. History
• Age – some of the ILDs are more common in certain age
groups
– Sarcoidosis, CTDs-associated ILDs, LAM, inherited forms of ILD,
and pulm LCH commonly present b/n ages of 20-40 yrs
– Most patients with IPF are over the age of 50yrs
• Gender
– Female
• LAM and tuberous sclerosis
• LIP, CTDs associated ILDs except RA
– Male
• IPF
• ILD associated with RA
• pneumoconiosis

15. Age at onset of presentation in
different interstitial lung diseases

16. • Onset of symptoms
– Acute presentation- unusual, days to weeks
• Acute interstitial pneumonia
• Eosinophilic pneumonia
• Hypersensitivity pneumonitis
• Cryptogenic organizing pneumonia
• NB- infectious causes of interstitial infiltrates should be ruled
out
– Subacute- weeks to months
• Can occur in all ILDs
• Sarcoidosis, drug induced ILDs, alveolar hemorrhage sxxs,
SLE associated pneumonitis

17. – Chronic presentations- months to years
• Most ILDs present with longstanding sxs
• IPF
• Sarcoidosis
• Pneumoconiosis
• PLCH and CTDs
• Important ddxs are COPD and chronic HF
– Episodic presentations- unusual, but can occur in
• Eosinophilic pneumonia, hypersensitivity pneumonitis, COP,
and pulm hemorrhage sxx
– Hypersensitivity pneumonitis and sarcoidosis can have
acute, subacute, or chronic presentations

18. • Past medical history
– CTDs, IBD, or malignancy
– Medications and prior irradiation
– Immunosuppression
– Hx of allergy and asthma
• Smoking history
- some ILDs occur largely among current or former smokers
• PLCH
• DIP
• RB-ILD
• IPF
– Active smoking can contribute to complications in pts with
goodpasture’s sxx

19. • Family history
– Autosomal dominant pattern of inheritance has been reported
for familial IPF, tuberous sclerosis, and neurofibromatosis
– Autosomal recessive pattern of inheritance has been identified
for Niemann-Pick disease, Gaucher’s disease, and Hermansky-
pudlak sxx
• Occupational and environmental exposures
– Review of home and work environment
– A strict chronologic listing of the pt’s lifelong employment
– The degree of exposure, duration, latency of exposure, and the
use of protective devices

22. • Symptoms- most are nonspecific, but some will help to narrow differential
– Dyspnea- sarcoidosis, silicosis, and PLCH may have extensive parenchymal lung
disease on CXR without significant dyspnea
– Cough-particularly bothersome in conditions that involve the airways like
sarcoidosis, PLCH, hypersensitivity pneumonitis
– Hemoptysis- diffuse alveolar hemorrhage sxx, PLCH, granulomatous
vasculitidis
– Wheezing – lymphangitic carcinomtosis, chronic eosilophilic pneumonia,
respiratory bronchiolitis,HP Sarcoidosis
– Chest pain- CTDs, sarcoidosis, or pneumothorax(from LAM,LCH)
– Extrapulmonary symptoms

23. Physical examination
• Findings are nonspecific, except the extrapulm ones suggesting the
underlying sytemic disorder
• Tachypnea
• Bibasilar end inspiratory crackles
• Accentuated P2, evidence of right side heart failure
• Clubbing- common in IPF and asbestosis, but rare in sarcoidosis and
hypersensitivity pneumonitis
• Extrapulmonary findings of systemic disease

24. Extrapulmonary physical findings in
the interstitial lung diseases

25. Diagnostic testing
• Lab tests
– CBC with differential
– U/A, BUN, Cr
– RVI screening
– ANA, RF
– ANCA, anti-BM antibodies
– CRP, ESR
– ACEs
• ECG
• Echocardiography

26. Chest X-ray
• Reticular pattern is the most common finding
• Nodular and reticulonodular pattern can also be seen
• The correlation b/n CXR abns and clinical or histopathologic
stage of the disease is generally poor.
• The presence of honeycombing portends poor prognosis
• Could be normal in 10% of pts with ILD, esp hypersensitivity
pneumonitis

29. • Certain radiologic patterns give important clues to specific etiologies
• Other clues include changes in lung volumes, disease distribution, and
associated findings, including pleural and LN inv’t
• The main radiologic patterns seen in DPLDS include
– Reticular
– Nodular-including micronodular and miliary
– Linear- septal or kerley’s
– Reticulonodular
– Destructive
– Alveolar
– Bronchial
– Arterial patterns

30. • Reticular pattern
– Acute diseases
• Acute pneumonia in CTDs
• Allergic pneumonitis
– Chronic diseases
• All idiopathic interstitial pneumonias
• CTDs
• Asbestosis
• Radiation pneumonia
• Drug reactions
• LAM

32. • Micronodular patterns –
seen infrequently
– Early stages of
pneumoconiosis
– Alveolar microlithiasis
• Nodular pattern
– Usually seen in
granulomatous lesions
– Sarcoidosis
– Pneumoconiosis
– Pulm hemosiderosis
– Neoplasms
– Infectious causes- tbc, fungal
infections

33. • Linear opacities- kerley
lines
– Due to thickening of the
interlobular septa
– Frequently seen in LV
failure
– Can be seen in
lymphangitic
carcinomatosis, asbestosis,
RBILD and viral infections

34. • Lung volumes
– Loss of lung volume is a frequent feature of all ILDs
– Some ILDs are associated with normal or large lung
volumes due to airflow obstruction or cystic changes
• PLCH
• Sarcoidosis
• LAM
– Low lung volumes can also represent the first
manifestation of ILD

36. • Disease distribution
– The anatomic distribution of lung disease can greatly
facilitate the approach to ddx
– Upper zone lung disease
• Sarcoidosis
• Pneumoconiosis except asbestosis
• PLCH
• Radiation fibrosis
• Infectious causes- tbc and fungal disease
• Ankylosing spondylitis

38. • Basal lung disease
– DIP
– NIP and fibrosis
– IPF/UIP
– Asbestosis
– Scleroderma
– Rheumatoid arthritis
– Drug reactions
• Central, perihilar disease
– Sarcoidosis
– Lymphoma
– Kaposi sarcoma
• Peripheral lung disease
– IIPs
– Asbestosis
– Eosinophilic lung disease
– Graft-vs-host disease
• NB- advanced stages of any
infiltrative lung process can
involve both lungs diffusely

39. Associated findings
• Pleural disease
– Pneumothorax
• PLCH
• LAM
– Pleural effusions
• Metastatic malignancies
• CVDs esp RA and SLE
• LAM
– Pleural plaques-
accompany 30-50% of pts
with longstanding asbestos
exposure
• LN involvement
– Sarcoidosis
– Lymphoma
– Pneumoconiosis
– Malignancy
– Tbc and fungal pneumnia
• Cor pulmonale
– Common manifestation of
end-stage disease

41. HRCT
• For early detection and confirmation of ILD
• Better assessment of the extent and distribution of disease
• Avoids the need for biopsy in those pts with IPF
• Certain features suggest specific diagnosis
– LAP with upper lobe inv’t- sarcoidosis and other granulomatous
lesions
– Pleural plaques with linear calcification- asbestosis
– Subpleural and bibasilar reticular opacities associated with
honeycomb changes and traction bronchiectasis- IPF, RA
associated ILD, or chronic hypersensitivity pneumonitis

43. Pulmonary function testing
• Spirometry
– Assess the extent of pulmonary involvement
– Most ILDs have a restrictive pattern
• Reduced TLC, FRC, and RV
• FEV1 and FVC- reduced
• FEV1/FVC ratio- normal or increased
– Some ILDs can have obstructive pattern
• Sarcoidosis
• LAM
• Hypersensitivity pneumonitis
• PLCH
• Tuberous sclerosis
• Combined COPD with ILD
– Have prognostic value in pts with IIPs, esp IPF and NSIP

44. • Diffusing capacity (DLCO)
– Reduced DLCO is a common finding
– The severity of DLCO doesn’t correlate well with disease
prognosis
• Gas exchange at rest and during exercise
– Resting arterial blood gases may be normal in early ILD
– Normal PaO2 at rest doesn’t rule out significant hypoxemia
during exercise or sleep
– Exercise testing- 6MWT
• To follow ILD activity and responsiveness to Rx

45. • Bronchoalveolar lavage (BAL)
– Pts with hemoptysis
– Acute onset ILD
– Certain causes of ILD
• Sarcoidosis
• Hypersensitivity pneumonitis
• PLCH
– Suspicion of infectious causes
– No role in IPF
– No role in the assessment of ILD progression or
response to therapy

46. • Lung biopsy
– The most effective method for confirming the diagnosis and assessing
disease activity
– Done if less invasive evaluations are not sufficient to make the correct
dx
– Atypical or progressive sns and sxs
• Age <50yrs
• Fever, wt loss, hemoptysis
– Atypical radiographic features
– Rapid clinical deterioration
– Sudden change in radiographic appearance
– Relative C/Is
• Serious CVDs
• Honeycombing and other radiologic evidence of diffuse end-stage disease
• Severe pulm dysfunction and elderly

47. ILD diagnostic algorithm

48. Treatment
• Goal
– Reduce further lung damage
• Permanent removal of the offending agent
• Early identification and aggressive suppression of the acute and
chronic inflammatory process
– Therapy doesn’t reverse fibrosis
• Identify and Rx treatable causes
• Hypoxemia- supplemental O2
• Management of cor pulmonale
• Pulmonary rehabilitation

49. • Drug therapy
– Glucocorticoids
• For sxic ILD pts
• Start prednisone 0.5-1mg and taper slowly
• Rapid tapering or a shortened course can result in recurrence
– Cyclophosphamide and azathioprine
• If no response to steroids
• IPF, vasculitis, progressive systemic sclerosis
– Methotrexate, colchicine, penicillamine and cyclosporine
• If the above measures fail or not tolerated
• Anti fibrotic therapy
• Lung transplantation

50. References
• Harrison’s principle of internal medicine,21th
e
• Uptodate 2023
• Current diagnosis and treatment in pulmonary
medicine

51. thank you!!!