Case 1: Familial IPF Case Presentation: Familial IPF - PowerPoint Presentation

Slide1

Case 1: Familial IPF Slide2

Case Presentation: Familial IPF

56-year-old Hispanic female with a family history of aortic aneurysm underwent a routine chest CT to assess her aorta

No respiratory symptoms

Medical history

h/o SVT

Type 2 diabetes mellitus

Hypertension

Iron-deficiency anemia

Hypothyroidism

Medications:

atorvastatin

;

metformin

;

levothyroxine

;

irbesartan

; aspirin

Habits: Lifetime non-smoker; non-drinker

No unusual pets or exposures

Family history of lung diseaseSlide3

Maternal Family TreeSlide4

CT

CT (not HRCT) obtained on 10/23/07 is shown on the following slide

CT shows ill-defined reticular opacities (arrows)

Because the scan is not high-resolution, some of the abnormalities appear to be of ground-glass opacity, but this is not likely the case

The abnormality involves all levels shown, including the upper lobes

The CT findings are consistent with UIP and IPF

Because ground-glass opacity may be present, NSIP must also be consideredSlide5
Slide6

Clinical Course

Patient remained asymptomatic and continued to work as an HR specialist

About 3 months prior to evaluation, the patient noticed the onset of some mild DOE while going up stairs and sometimes while getting dressed. This was also associated with the onset of a dry cough

Saw pulmonologist

Obtained a CT of the chest

Recommended a VATS biopsy, based on the family history of IPF and “presumed”

sarcoidosisSlide7

CT

CT 2 years later (next slide) shows progression of the ill-defined opacities which are diffuse and strikingly peripheral in distribution; they are likely reticular in nature

The abnormality remains consistent with UIP and IPF, or NSIP, but would be very unusual with sarcoidosis

Sarcoidosis typically results in small or large nodular opacities, which are

peribronchial

and subpleural in distribution, and predominate in the upper lobesSlide8
Slide9

Fibroblast Foci (ff)

Normal

Lung

F

F

Fibrosis (F)

F

Microscopic

honeycombing

F

SLB Reveals UIP:

Image ASlide10

Fibroblast

Foci (ff)

Temporal Heterogeneity in UIP:

Image BSlide11

ff

Type 2 cells

F

Fibroblast Focus:

Image CSlide12

Histopathologic Findings

At low magnification (Image A), coarse fibrosis appears to surround areas of more normal lung. All of the features required for a diagnosis of UIP are illustrated in this image. The alternating zones of fibrosis (F) and normal lung (N) are accentuated by fibroblast foci (ff).

Endstage

microscopic lung remodeling referred to as “microscopic honeycombing” (

mh

) is nearly always present in UIP

Temporal heterogeneity in UIP (Image B). The transitions from fibrosis to normal lung are nicely illustrated. A few fibroblast foci (ff) are evident

The fibroblast focus in Image C has a parallel arrangement of immature fibroblasts covered by a thin layer of pink-appearing reactive type 2 cells (t2). Note the coarse fibrosis (F) underlying the fibroblast focusSlide13

Serial PFTs

10/20/09

3/8/10

(

Symptom

onset)

5/26/10

FVC

1.15

0.91

0.92

FVC%

41

32

33

FEV

1

1.02

0.78

0.88

FEV

1

%

44

33

38

TLC

4.01

3.68

1.83

TLC%

87

80

40

DL

CO

7.5

7.9

6.5

DL

CO

%

32

34

28Slide14

Clinical Course

Referred to ILD clinic

6MWT on room air

Resting SpO

2

= 100

Walked 417 meters on room air,

desaturation

to 93%

Borg score = 4

HR increased from 80 to 105, recovered to 91 one minute after exercise

Diagnosis of familial IPF confirmedPossible that family members with “presumed” sarcoidosis could have had IPF instead

Work-up for potential lung transplantation recommended and initiatedSlide15

Familial IPF Summary

Familial IPF accounts for less than 5% of total IPF cases

It is characterized by two or more cases of idiopathic interstitial pneumonia in first-degree relatives

Autosomal dominance with reduced penetrance is likely

Not all of the genes associated with familial pulmonary fibrosis are known. Mutations have been identified in about 10% of individuals with familial pulmonary fibrosis

Surfactant protein C

TERT (telomerase reverse transcriptase)

TERC

(

telomerase RNA component

) Slide16

Case 2: Inflammatory Bowel Disease (IBD)Slide17

Case Presentation

78-year-old female in relatively good health presented in 2005 with diarrhea, abdominal pain, and fever

Colonoscopy revealed inflammatory colitis (ulcerative colitis) and she was treated with mesalamine

Two months later she developed fever, diarrhea, and flu-like illness associated with cough and bibasilar crackles on physical examination

Chest radiograph revealed minimal increase in chronic interstitial markings

A diagnosis of therapy-related pneumonitis was established clinically

Mesalamine was discontinued and budesonide enemas substitutedSlide18

Case Presentation

Medical History

Ex-smoker, 7.5 pack-years

Fistula repair 20 years before

History of psoriasis

Family history of Crohn’s disease

Examination

Physical exam

BP 149/81 P 105 R 14

Weight = 116 lb (52.617 kg)

SpO2 = 97% on oxygen supplementation

Pertinent findingsBibasilar rales, rare squeaksNo clubbingSlide19

CT 12/19/05

Upper Lobes

CarinaSlide20

CT 12/19/05, Lower Lobes

Slide21

CT 12/19/05

Upper lobe tubular bronchiectatic changes

Surrounding lung with hazy opacities

Patchy areas of similar appearance in lower lobesSlide22

Clinical Course 2006-2008

Recurrent febrile episodes associated with abdominal pain and profuse mucousy diarrhea

In January 2008, she presented with cough, phlegm expectoration, dyspnea on effort, hypoxemia, fatigue, and malaise

No associated fever, chest pain, arthralgias, or hemoptysis

She was treated with moxifloxacin and low-dose corticosteroids

She improved but did not regain fully her previous functional status

Dyspnea on exertion progressed

Repeat CT scan in May 2008 showed progressive changes: increased interstitial markings and diffuse ground-glass opacities Slide23

CT 5/20/08, Upper LobesSlide24

CT 5/20/08, CarinaSlide25

CT 5/20/08, Lower LobesSlide26

Radiology Summary

CT findings

Ground glass densities

Bands of interstitial changes

Focal honeycombing

Traction bronchiectasis

Peribronchial inflammation

Distribution: not predominantly peripheral

CXR (data not shown)

Increased interstitial markings

Relatively well-maintained lung volumesSlide27

Clinical Course 2008

Pulmonary function, O

2

saturation, and HRCT were abnormal

Test results for collagen vascular disease, vasculitis (ANCA), and HP were negative

Mild hypogammaglobulinemia

6/25/08 VATS lung biopsy

Date

FVC

FEV

1

TLC

DL

CO

Vol, L

%

predVol, L

%

pred

%

pred

%

pred

4/25/07

2.1

86

1.69

102

73

55

5/20/08

1.68

71

1.39

79

70

34

6/11/08

1.81

76

1.55

88

35Slide28

Medium power image of small

airway

Peribronchial Chronic Inflammation and Bronchiolar Metaplasia of Adjacent Alveolar Spaces

Image courtesy of Dr. MB BeasleySlide29

Chronic Inflammation and Remodeling; Bronchiolar Metaplasia

Image courtesy of Dr. MB Beasley

Higher power view of small airway Slide30

Image courtesy of Dr. MB Beasley

Foamy Macrophages in Alveolar Spaces

Suggest Airway ObstructionSlide31

Image courtesy of Dr. MB Beasley

Subpleural Architecture

: Focal Fibrosis and EmphysemaSlide32

Histopathology

Sampling

Right upper, middle, and lower lobe

Wedge biopsies

Findings

Chronic interstitial pneumonia

Focal granulomatous inflammation

Interstitial fibrosis

Review by independent pathologist

Diagnosis confirmed

Process is accentuated around bronchioles suggesting HP or infection such as mycobacteria

No serologic evidence of HP No growth of mycobacteria detectedSlide33

Corticosteroid treatment, improved condition

Relapse of respiratory symptoms and radiographic findings with lowering of corticosteroids

Activity of IBD associated with respiratory symptoms

Pulmonary exacerbations managed with

Immunosuppressive agents

IVIG infusions

Periodic antibiotics

Chronic macrolide treatment

Mucolytics

Increased doses of corticosteroids

Clinical Course 2008-2010Slide34

PFT Update

Date

FVC

FEV

1

TLC

DL

CO

Vol, L

%

pred

Vol, L

%

pred

%

pred

%

pred

4/25/07

2.1

86

1.69

102

73

55

5/20/08

1.68

71

1.39

79

70

34

6/11/08

1.81

76

1.55

88

35

4/28/10

2.07

83

1.74

94

48

7/21/10

1.89

75

1.53

83

54

Decline of PFTs on 7/21/10 coincided with activity of IBD, prednisone dose increasedSlide35

Clinical Course Summary

2005 initial presentation

Resolution of acute symptoms but persistence of abnormal CT

2007 exacerbation of pulmonary symptoms

Treatment of IBD and pulmonary manifestations with steroids

2008 exacerbation – VATS biopsy

Treatment with corticosteroids, immunosuppressive agents (IS), macrolides

2008-2010 management of disease with steroids, IS, IVIG, antioxidants, and macrolides leads to clinical stabilitySlide36

Case Summary

Onset of pulmonary disease after many years of inflammatory bowel disease

Pulmonary disease manifested initially with mesalamine treatment

Lung disease is airway-centered but with evidence of ILD

Response and stabilization with multidrug therapySlide37

Pulmonary Aspects of IBD

Pulmonary manifestations more common in ulcerative colitis than Crohn’s

Airways more commonly involved than parenchyma

Pulmonary symptoms usually follow IBD diagnosisSlide38

Pulmonary Aspects of IBD

Symptoms

1,2

Present in 44–48% of patients with IBD

Cough, phlegm expectoration, wheezing, and dyspnea

Association with asthma and IBD-Asthma more severe in this setting

PFT abnormalities

Most common: decreased diffusing capacity

Airway reactivity may be present (detected with methacholine challenge)

Songür N, et al.

J Clin Gastroenterol

. 2003;37:292-298.

Douglas JG, et al. Respir Med. 1989;83:389-394.Slide39

Pulmonary Aspects of IBD: HRCT

Abnormalities in 53% of patients with IBD

1

Air trapping, GGO, peripheral reticular opacities, and cysts

Nodules

Bronchiectasis

COP and ILD patterns may also be detected

Songür N, et al.

J Clin Gastroenterol

. 2003;37:292-298.Slide40

Pulmonary Aspects of IBD

Bronchiectasis

Most common pulmonary manifestation of IBD (in ~66% of patients with airway manifestation)

Exacerbations may occur in close proximity to colonic resection

Small airways less frequently involved than larger airways

With small airway involvement, bronchiolitis is the most common finding

Can be associated with granuloma formation

IBD pulmonary manifestations may be confused with HP or infection

Upper airways are least frequently involved

Parenchymal involvement

Histologic patterns reported: chronic organizing pneumonia, HP, desquamative interstitial pneumonia, NSIP, fibrosing lung diseaseSlide41

Pulmonary Aspects of IBD: Histology

Features

Microscopic granulomas sometimes present

Nodules (may be necrobiotic)

Airway-centered inflammatory process

Bronchiectasis

Histologic patterns similar to the idiopathic interstitial pneumonias can also be seen

The predilection for airway involvement and the degree of associated inflammation contrasts with UIP in cases with parenchymal manifestationsSlide42

IBD Summary

Thoracic manifestations of inflammatory bowel disease are frequent and underdiagnosed

Bronchiectasis and airway abnormalities most common

Pulmonary function studies: decreased diffusing capacity

Pathology: interstitial and airway inflammation, granulomas may be present

IBD therapy may induce lung disease

Sulfasalazine

Mesalamine

Methotrexate

Treatment of IBD-associated lung disease

Corticosteroids

Immunosuppressive agents

Disease-modifying agents to treat IBD