This document discusses non-specific interstitial pneumonia (NSIP), a type of interstitial lung disease. It provides details on: 1. The characteristic CT findings of NSIP including ground glass opacities, irregular linear opacities, and lower lobe predominance with sparing of the subpleural lung. Honeycombing is uncommon. 2. NSIP can be difficult to distinguish from other interstitial lung diseases on CT alone, and a multidisciplinary approach including biopsy may be needed. The extent of honeycombing seen on CT helps distinguish NSIP from idiopathic pulmonary fibrosis. 3. The prognosis of NSIP depends on the subtype, with fibrotic NS

1. Presented By Dr Vrishit Saraswat
2nd Yr Resident
Guided By Prof. Dr Dharmraj Meena
Department of Radiodiagnosis

2.  Group of diffuse parenchymal lung diseases
 Unknown etiology
 Varying degrees of inflammation and fibrosis.
Four types ( ATS/ERS-2013)
1. Chronic Fibrosing IIPs – IPFUIP and NSIP
2. Acute or sub acute IIPs – AIP and COP
3. Smoking related IIPs – RB-ILD and DIP desquamative
4. Rare IIPs - LIP and PPFE pleuro parenchymal fibro elastosis
UIP /IPF acounts for 50-60% of all cases

3. Acc. To ATS/ERS, diag of IIP given by =
clinical + Radiological + histological
 For ex- UIP is a type of lung reaction pattern to
any injury. It may occur secondary to dust
exposure, drugs or after HP or with collagen
vascular dx.

4.  Male + >50yrs + exertional dyspnea + basal
crackles + finger clubbing .
 Chronic condition
 Extensive fibrosis
 Associated with radiological pattern of UIP.

5. Repetitive microinjuries to lung
Fragmentation of type I alveolar
cells
Disruption of basement
membrane
Release of inflam mediators responsible
for migration of fibroblast
Exaggerated production of extracellular
matrix by fibroblastic foci
Destruction of
lung
parenchyma

6.  Temporal heterogenicity
different stages in the evolution of
fibrosis, a combination of old lesions, active lesions
and normal lung ; i.e. aggregates of proliferating
fibroblasts and myofibroblasts that represent
microscopic zones of acute lung injury set against a
backdrop of chronic fibrosis and honeycombing
with areas of normal lung parenchyma.
The fibrosis and honeycombing typically involves
subpleural, paraseptal and basal lung regions .

8.  4 histopathological criterias
1. Marked fibrosis +/- Honeycombing.
2. Patchy involvement of lung
3. Presence of fibroblastic foci
4. Absence of features s/o an alternative diag.
Presence all above 4 criterias set the diagnosis of
IPF histologically.

10.  The international official ATS/ERS/JRS/ALAT
statement on IPF published in 2011 established
that a diagnosis of UIP can often be made on
HRCT, obviating lung biopsy.
 In patients with characteristic UIP findings on
HRCT, the diagnosis of IPF requires exclusion
of other known causes of interstitial lung
disease such as domestic and occupational
environmental exposures, connective tissue
disease, and drug toxicity.

11.  Early stage - Bilateral irregular linear opacities
causing a reticular pattern , involving lower lung
zone.
 In end stage- extensive honeycombing.
1. Marked fibrosis- On HRCT, IPF is characterized by
intralobular interstitial thickening , results in
reticular pattern in subpleural region - typical
pathological feature of UIP. Dilated and distorted
centrilobular bronchioles are frequently visible
within the areas of reticulation, i.e., traction
bronchiolectasis.

13. 2. Honeycombing- Honeycombing is critical for
making a definitive diagnosis on HRCT,
individual lobules are no longer visible.
Honeycomb cysts usually range from 3 to 10
mm in diameter, but they can be as large as 2.5
cm. The frequency of honeycombing varies
with the severity or stage of the disease.
Findings of honeycombing and fibrosis are
most often symmetric.

15.  GGO is commonly seen on HRCT , but less
extensive than reticulations
 Areas of ground-glass opacity are associated
with reticulation and therefore probably reflect the
presence of microscopic fibrosis. However,
some of the areas of ground-glass opacity are
not associated with findings of fibrosis and
therefore are most consistent with active
inflammation.

17. 3. Patchy involvement- Areas of mild and severe
fibrosis and normal lung are often present in
the same patient, in the same lung, and in the
same lobe.

18.  A confident diagnosis of IPF on HRCT requires clinical
exclusion of known causes of UIP and the presence of all of
the following four criteria: reticular pattern, honeycombing,
subpleural and basal predominance, and absence of atypical
features.
 Atypical features-
1. upper or mid-lung predominance,
2. peribronchovascular predominance
3. consolidation,
4. extensive ground-glass opacities,
5. profuse micronodules,
6. discrete cysts (multiple, bilateral, away from areas of
honeycombing),
7. diffuse mosaic attenuation/air trapping (bilateral, in three or
more lobes)

19.  Occasionally, fine linear or small nodular foci
of calcification are seen within areas of fibrosis
as a result of ossification; disseminated
dendriform pulmonary ossification on HRCT.
It has very low incidence, but is seen in pts
with IPF and newer in pts with NSIP

21.  Patients with IPF have an increased risk of lung
cancer(5X) and tuberculosis; patients who are
receiving corticosteroids are at an increased
risk of opportunistic infection particularly
Pneumocystis jirovecii.
 Patients with IPF and active tuberculosis,
HRCT demonstrated peripheral nodules or
mass-like lesions. Typical patterns of active
tuberculosis, including patchy multifocal
consolidation, tree-in-bud pattern, and
centrilobular nodules, were uncommon.

23.  Follow-up studies have shown progressive
increase in the extent of reticulation and
honeycombing 1 year or more after diagnosis.
 patients with IPF develop acute respiratory
worsening d/t secondary pneumonia,
pulmonary embolism, pneumothorax, or
cardiac failure. When any cause cannot be
identified, the term acute exacerbation of IPF is
used.

24.  The histologic findings of acute exacerbation of IPF
consist of diffuse alveolar damage (DAD). The
HRCT manifestations consist of extensive bilateral
ground-glass opacities and/or consolidation
superimposed on reticulation and honeycombing.
Patients with acute exacerbation have a poor
prognosis with mortality exceeding 60%.
 The main differential diagnosis of acute
exacerbation on HRCT in patients with known IPF
and acute clinical deterioration is opportunistic
infection, particularly P. jirovecii pneumonia (PCP).
In the context of IPF, the HRCT findings of PCP
may be indistinguishable from those of acute
exacerbation.

25. 1

26. 2

27.  Among patients with IPF, a HRCT showing
characteristic features of IPF, namely,
honeycombing, was associated with worse
survival than a HRCT showing no honeycombing.
 On multivariate analysis, a high fibrotic score
(extent of reticulation plus honeycombing) and an
initial low DLCO were identified as associated
with increased death risk. Overall, these various
studies demonstrate that the prognosis of IPF is
worse than that of NSIP and that the prognosis in
IPF is influenced by the extent and severity of
fibrosis.

28.  Surgical lung biopsy has limitations b/c the region
sampled may not be representative of the lung as a
whole, and the presence of inflammation may be
missed.
 Various studies showed 60-70% sensitivity and
approx 90% specificity in diagnosing IPF on
HRCT.
 Based on these various studies, it is now well
accepted that in the appropriate clinical setting the
presence of characteristic HRCT findings allows
confident noninvasive diagnosis of IPF obviating
lung biopsy.

29.  Confident diagnosis of honeycombing requires
presence of clustered cystic airspaces measuring 2
mm to 1 cm in diameter that have well-defined
thick walls and are located adjacent to the pleura.
They must be distinguished from traction
bronchiolectasis, which may have a similar
appearance, but is typically located a few
millimeters or more from the pleura.
 It is important to note that in the correct clinical
setting a diagnosis of IPF is not excluded by HRCT
findings more suggestive of an alternate diagnosis.
inBiopsy proven IPF
 In these atypical IPF cases, the most common
HRCT diagnoses were NSIP, chronic HP, and
sarcoidosis .

32.  Homogenous expansion of alveolar walls by
varying amounts of interstitial inflammation
and fibrosis.
 Relative temporal and geographical
homogenicity.
 Women
 Non smoker
 Age less than 50 yrs
 Honeycombing is uncommon

33.  2 types (a) cellular NSIP
(b) Fibrotic NSIP (more common)
 Fibrosis may involve alveolar septa,
peribronchivascular interstitium, interlobular
septa and visceral pleura.
 Prognosis of fibrotic NSIP is worse , cellular
NSIP has good prognosis.
 HRCT finding may show both, airspace and
interstitial patterns.

34. C

35.  Typical HRCT findings- GGO , irregular linear
opacity ( reticulations ), traction bronchietasis.
 GGO found in patients , changed into reticular
opacity after few years.
 Honeycombing, if present, tends to be mild
 Lower lobe predominance is common. Upper
lobe is uncommon in NSIP and should suggest
another diagnosis (chronic HP, sarcoidosis)

36. F

37.  Characteristic finding of NSIP is relative
sparing of the immediate subpleural lung in
dorsal region of lower lobe.
 CT findings tend to improve with treatment in
pts who mainly have GGO predominance (cellular;
airspace) than pts who have predominant fibrosis
on previous scans.
 The majority of patients who show progression
of fibrosis on follow up ; a significant minority
progress to UIP pattern.

38. M

39.  Abnormalities seen on HRCT in NSIP can
mimic with :-
(a) UIP (predominantly lower lobe reticulations)
(b) HP, RB-ILD (predominantly GGO)
(c) BOOP(when there is extensive consolidation)
 Multivariate logistic regression analysis
showed that the most useful finding for
distinguishing IPF from NSIP was the extent of
honeycombing. The average extent of
honeycombing was 4.4% of parenchyma in IPF
and less than 1% in NSIP.

40.  Lower lobe predominance
 Traction bronchiectasis
 Subpleural sparing
 Extensive reticulation and
fibrosis

41.  Various studies demonstrate that HRCT allows
distinction of NSIP from IPF and chronic HP in
many patients. However, although the presence of
predominantly peripheral and basal
honeycombing in the appropriate clinical setting
often allows a confident diagnosis of IPF on HRCT,
a confident diagnosis of NSIP requires surgical
biopsy and a dynamic multidisciplinary approach
with input from clinicians, radiologists, and
pathologists . It is important to note that even a
histologic diagnosis of NSIP does not establish a
final diagnosis.

44.  HRCT finding of patchy or subpleural ground-
glass opacity, with or without reticulation,
should suggest a likely diagnosis of NSIP
rather than UIP. Generally, lung biopsy is
recommended in this setting.

45.  In cases where diagnosis cannot be made because
of overlap of CT and histological findings; Chrug
& Muller proposed a three seperations on HRCT
for chronic interstitial diseases.
(A) Air space opacification(GGO or consolidation) –
COP / Cellular NSIP/DIP / Sub acute HP – good
prognosis.
(B) Diseases manifesting extensive GGO with mild
reticulation(>25% of lung parenchyma)- mixed
NSIP / Chronic HP.
(C) Predominant Reticulations – fibrotic NSIP/ UIP.