Biopsy not required for Idiopathic Pulmonary Fibrosis

Dr. Altay Şahin Hacettepe University

IPFIPF is an idiopathic interstitial pneumonitis is an idiopathic interstitial pneumonitis, , which which has the histological presentation of UIP and leads has the histological presentation of UIP and leads to chronic fibrosis to chronic fibrosis

UIP pattern is not specific for IPF, can be also found UIP pattern is not specific for IPF, can be also found in Collagen Vascular Disease (CVD) and even in Collagen Vascular Disease (CVD) and even sarcoidosissarcoidosis

Major criteira for the diagnosis: A) the other causes Major criteira for the diagnosis: A) the other causes for ILD should be excluded, B) PFT defect, for ILD should be excluded, B) PFT defect, inadequate gas exchange, C) consistent HRCT inadequate gas exchange, C) consistent HRCT findings, D) BALF analysis not supporting an findings, D) BALF analysis not supporting an alternative diagnosis, a) Age >50 years, b) acute alternative diagnosis, a) Age >50 years, b) acute emergence of dyspnea, c) duration of disease >3 emergence of dyspnea, c) duration of disease >3 months, d) months, d) BibaBibassillillaar inspr inspiratuariratuar crackles crackles

Gregory B. Diette; John C. Scatarige; Edward F. Haponik; Barry Merriman; Elli.. Do High-Resolution CT Findings of Usual Interstitial Pneumonitis Obviate Lung....Respiration; Mar/Apr 2005; 72, 2;134-141

Experienced with the help of HRCT and clinical presentation radiologist can diagnose IPF, LAM, Eosinophilic granuloma, sarcoidosis and PCP with a high rate of correct result.

Biopsy from different lobes may show different histopathology upto 26% of cases

Most of the clinicians in US accept HRCT in the diagnosis of IPF, Asbestosis, Silicosis, ve bronchiectasis. Only 3% does not accept HRCT instead of biopsy.

Only 60% of the clinicans have read ATS/ERS guide, 10% were aware, while the others were unaware

Fishbein MC. Chest 2005;128(5):520S-525SFishbein MC. Chest 2005;128(5):520S-525S Peckham RM, et al. Respiration Peckham RM, et al. Respiration 2004;71:165-1692004;71:165-169

Board certified specialists evaluated the clinical Board certified specialists evaluated the clinical and HRCT findings in 26 patients undergoing and HRCT findings in 26 patients undergoing surgery and put the diagnosis of UIP in 14, surgery and put the diagnosis of UIP in 14, NSIP in 5, sarcoidosis in 2, malignancy in 2, NSIP in 5, sarcoidosis in 2, malignancy in 2, COP in 2, respiratory bronchiolitis associated COP in 2, respiratory bronchiolitis associated ILD and end stage fibrosisILD and end stage fibrosis

For the diagnosis of IPF: Sensitivity was 71%, For the diagnosis of IPF: Sensitivity was 71%, positive predictive value was 77%, spesifity positive predictive value was 77%, spesifity was 75%, negative predictive value was 69%, was 75%, negative predictive value was 69%,

there was 4 false negative and 3 false positive there was 4 false negative and 3 false positive casescases

Kappa - Agreement >0.8: almost perfect agreement 0.6-0.8: substantial agreement 0.4-0.6: moderate agreement 0.2-0.4: fair agreement 0.0-0.2: slight agreement <0.0: poor agreement

Nicholson AG, et al. Interobserver variation between pathologist in diffuse parenchymal lung disease. Thorax

2004;59:500-505

Mean kappa for the first choice diagnosis was 0.38, and improved to 0.43 when the biopsies were received from multiple lobes

Weighted kappa, which shows the diagnostic probability had a mean of 0.58 with a range of 0.40-0.75

Confidence in diagnosis was low in 18% of the biopsies

Difference between the pathologists in the diagnosis of NSIP especially the differential diagnosis from IPF exceeded 50%

Irish Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Group, a subgroup of the British Thoracic Society Standards of Care Committee, A U Wells, N Hirani and on

behalf of the BTS Interstitial Lung Disease Guideline Interstitial lung disease guideline Thorax 2008;63;v1-v58

In the UK histopathological panel, primary diagnosis proportion was too low to be for the clinical use. For the majority of the cases histopathological features were indistinct, and consistent with two or more of the diagnoses.

Another important problem was that the biopsy was not representative of the predominant disease. This is particulat for the distinction between UIP and NSIP.

With consistent clinical presentation and HRCT findings IPF can be diagnosed in 70% of the cases. For these cases surgical biopsy does not have an additional benefit. Surgical biopsy by itself is not significant without the clinical and radiological findings.

Final diagnosis changed by 50% for the cases which lack the typical clinical and HRCT findings.

Idiopathic Interstitial Pneumonia: What Is the Effect of a Multidisciplinary Approach to Diagnosis? Kevin R Flaherty; Talmadge E King Jr; Ganesh Raghu; Joseph P Lynch III; et al American Journal of Respiratory and Critical Care Medicine; Oct 15, 2004; 170:904-910

58 IIP cases diagnosed with surgical lung biopsy were investigated ina a stepwise manner

Step 1: 3 clinicians and 2 radiologists independently reviewed HRCT findings and recorded their individual diagnoses

Step 2: 3 + standard clinical information and recorded their individual diagnoses

Step 3: + discussed HRCT findings with standard clinical information and recorded their individual diagnoses

Patologhists (n: 2) unaware of these information recorded their individual diagnosis

Step 4: + 2 pathologists independently reviewed and discussed HRCT findings with standard clinical information and pathological findings and recorded their individual diagnoses

Step 4: + a consensus was sought, in case of disrepancy each recorded their individual diagnoses

Agreement of the evaluations in these steps have been investigated

Idiopathic Interstitial Pneumonia: What Is the Effect of a Multidisciplinary Approach to Diagnosis? Kevin R Flaherty; Talmadge E King Jr; Ganesh Raghu; Joseph P Lynch III; et al American Journal of Respiratory and Critical Care Medicine; Oct 15, 2004; 170:904-910

Correct diagnosis % as compared to pathologists: Clinicians 17-27% less

with only HRCT review, 12-18% less with clinical infromation and radiologists’ discussion

Radiologists %38-44 less with with only HRCT review , 34-41% less with clinical infromation and clinicians ’ discussion Histopatolojik bilgiler

After the histopathological information clinicians 3-12% better, radiologists 10-12% better than the pathologists

Pathologist A Pathologist B

Consensus

IPF 27 28 30

NSIP 11 14 15

RBILD/DIP 1 1 3

HP 2 1 1

BD 7 4 4

Diğer 10 10 5

-0,6

-0,4

-0,2

0,0

0,2

A B C P R1 R2

HRCT

HRCT+C

HRCT+C D

HRCT+C+P

HRCT+C+P Cs

Correct diagnosis % (reference: pathologists

C: clinical information, D: discussion, P: pathology findings, Cs: consensus,

Thomeer M, et al. Eur Respir J 2008;31:585-591

36 investigators from 6 European countries examined 179 HRCT and 82 OLB/TBL. Local investiagators sent their speciamens to 2 pathological investigation committee. Evaluations were classified as Very Suggestive, Probable and Unlikely.

assessment of 512 HRCT : -67 Unlikely (12.6%), -203 Probable (38.2%), - 258 Very Suggestive (48.5%)

assessment of 44 OLB, 38 TBL specimens: - 76 Very Suggestive (42.7%), - 66 Probable (37.1%), - 33 Unlikely (18.5%)

UIP was diagnosed in 84% of the 82 biopsies, 92.7% of the 165 HRCT’s. When FVC (> 60% or <60%) was added to HRCT review correct diagnosis % increased to 100%.

Clinical diagnosis proportion: 87.2% Agreement was 0.40 in HRCT, and 0.30 in histology

Nicholson AG, et al. Thorax 2004;59:500-505 Raghu G, et al. Chest 1999;116:1168-Nicholson AG, et al. Thorax 2004;59:500-505 Raghu G, et al. Chest 1999;116:1168-1174 Hanninghake GW, et al. AJRCCM 2001;164:193-196 Ryu JH, et al. Mayo Clin 1174 Hanninghake GW, et al. AJRCCM 2001;164:193-196 Ryu JH, et al. Mayo Clin

Proc 2007;82:976-986Proc 2007;82:976-986

In UK, 10 pathologists retrospectively examined 133 lobar In UK, 10 pathologists retrospectively examined 133 lobar biopsy specimens of cases provided with age, sex and the biopsy specimens of cases provided with age, sex and the biopsy site information, without findings of infection,. biopsy site information, without findings of infection,.

Confidence in the primary diagnosis of the pathologists was Confidence in the primary diagnosis of the pathologists was around 5%. The agreement between the primary diagnosis around 5%. The agreement between the primary diagnosis of the pathologists was kappa: 0.38, and increased to of the pathologists was kappa: 0.38, and increased to kappa: 0.43 with confidence level >70%, when multiple kappa: 0.43 with confidence level >70%, when multiple biopsies were taken. For IPF agreement increased from biopsies were taken. For IPF agreement increased from kappa: 0.42 to 0.49. Kappas were 0.76 to 0.82 for kappa: 0.42 to 0.49. Kappas were 0.76 to 0.82 for sarcoidosis , and 0.29 to 0.32 for NSIP, respectively. For UIP sarcoidosis , and 0.29 to 0.32 for NSIP, respectively. For UIP and NSIP, the differences between pathologists were and NSIP, the differences between pathologists were significant in the end stage disease.significant in the end stage disease.

According to these results, distinction in According to these results, distinction in the histopathological diagnosis exists the histopathological diagnosis exists between routine pathological between routine pathological investigations. investigations.

Lettieri CJ, et al. Respiratory Medicine (2005) 99, 1425–1430

Histopathologicl Diagnosis Specialist Pathologist General Pathologist

Usual Interstitial Pneumonia 17 22

Non-Specific nterstitial Pneumonia 10 7

Sarcoidosis 4 0

Cryptogenic Organizing Pneumonia 3 3

Diffuse Alveoler Damage 2 1

Infecti on 2 1

Malignancy 2 0

other 5 10

Specialist Pathologists recorded distinct diagnoss in 52.3%, (kappa = 0.21). This caused a change in the treatment in 60%. Sensitivity and specificity of the general pathologists for IPF were 76.5% and 66.7%, respectively.

Visscher DW, Myers JL. Histologic spectrum of idiopathic interstitial pneumonias. Proc Am Thorac Soc 2006;3:322

Three major problems reaching a diagnosis of UIP, -The first is sampling, “indeterminate pathologic findings”, -Presence of fibrotic changes resembling UIP in other conditions, -Microscopic findings, that resemble other conditions.

These problems need for clinical and radiographic correlation

“This review is an attempt to address these controversies and doing so provide the pathologist with a straighforward and

practical approach to diagnosing the chronic interstitial pneumoniast”

Katzenstein ALA, et al. Human Pathology 2008;39:1275-1294

UIP Diagnostic Criteria 1. patchy involvement pattern of the parenchyma, non-uniform, distributed unevenly, 2. distorted structure, honey combing and scar, variable distribution of fibroblast foci and collagen deposition

UIP – can be mixed up with Asbestosis, HP, CVD, if the biopsy is taken from a single lobe small specimen could be consistent with NSIP. UIP has a heterogenous distribution.

Hipersensitivite Pnomonisi – can be mixed up with UIP. HP peribronchiolar epitheloid histiocyte non-nekrotising granuloma, mültinüclear giant cells, honey combing and fibrosis in advanced cases hardly distinguished from UIP.

Since there is no entity like unclassified interstitial fibrosis, pathologists have difficulty in recording an appropriate diagnosis. This is especially the case for fibrotic NSIP.

Katzenstein ALA, et al. Diagnosis of usual interstitial pneumonia and distinction from other fibrosing interstitial lung disease. Human Pathology

2008;39:1275-1294

Debate on the role of pathology in the diagnosis of IIP is one of the hot topics for the time being. More accurate and confirmed diagnoses are required for the consideration of novel, expensive treatments. Unclassified interstitial fibrosis cannot be offered as a diagnostic entity. This view could be inducing the pathologists to record an incorrect diagnosis.

Katzenstein ALA, et al. Human Pathology 2008;39:1275-1294

4.1. How is honeycomb change defined microscopically, and what is its relationship, if any,

to peribronchiolar metaplasia? 4.2. Because focal fibroblast proliferation is a feature of both fibroblast

foci and BOOP, can they always be distinguished 4.3. Are fibroblast foci specific for UIP? 4.4. Because NSIP tends to occur in individuals slightly younger than those

with UIP, and NSIP-like areas can be found in UIP, is NSIP an early form of UIP? 4.5. How much honeycomb change is too much to diagnose fibrosing

NSIP? 4.6. How much interstitial inflammation can be present in UIP before

another diagnosis is entertained?

Katzenstein ALA, et al. Human Pathology 2008;39:1275-1294

4.7. When discordant biopsy results are encountered from different lobes, which is the correct diagnosis?

4.8. Because biopsies from one lobe may occasionally show NSIP in cases with otherwise typical UIP in other lobes, can NSIP be accurately diagnosed on a biopsy taken from a single lobe?

4.9. Once fibrosis becomes extensive, how important is it to separate fibrosing NSIP, chronic HP, and scarred LCH from UIP?

4.10. Can idiopathic interstitial pneumonias other than UIP be diagnosed on TBB?

4.11. If the experts do not always agree, can these diseases be accurately diagnosed?

4.12. Can ordinary (nonpulmonary) pathologists diagnose UIP and related idiopathic interstitial pneumonias?

Katzenstein ALA, et al. Human Pathology 2008;39:1275-1294

4.13. By dividing interstitial lung disease into fibrotic predominant and cellular predominant

variants, are we reverting back to the classification schemes of the 1970s and 1980s?

4.14. What terminology should be used on the pathology report when diagnosing the idiopathic

interstitial pneumonias?

Fujita J, et al. Idiopathic non-specific interstitial pneumonia: as an ‘‘autoimmune interstitial pneumonia.’’ Respir Med 2005;99:234–240. Selman M, et al. Gene expression profiles distinguish idiopathic pulmonary

fibrosis from hypersensitivity pneumonitis. Am J Respir Crit Care Med 2006;173:188–198. Sahin H, et al. Chronic hypersensitivity pneumonitis: CT features comparison with pathologic evidence of fibrosis

and survival. Ra Radiology 2007;244:591–598. Investigations have revealed a predominant regulatory gene

of extracellular matrix and chemokine activity regardless of the form of IIP as UIP or NSIP

The slight difference between NSIP and UIP is surprizing for the clinical differences between IIP’s. Others showed different transcript levels. The transcripts of familial IIP, which constitutes severe forms is different from sporadic IIP’s.

In IPF, immune cells other than macrophages, and dendritic cells are active. There is an association between pathological pulmonary fibrosis and inflammation.

IPF Tanısı İçin Biyopsi Gerekmez Farklı loblardan alına biyopsi örnekleri birbirlerinden farklı

histopatolojik örnekleri temsil edebilmektedir. Histopatolojik bulgular NSIP ve HP ile benzerlik gösterebilir. Histopatolojik UIP tanısı ile klinik tablo ve hastalığın doğal

seyri, tedaviye yanıtı her zaman paralellik göstermez. Biyopsi tanısı zamanla değişebilmektedir. UIP’nin kesin tanısı için histopatolojik spesifik bir belirteç

yoktur. Hastalığın doğal seyri, klinik belirti bulguları, laboratuar

sonuçları, görüntüleme paternleri, tanı yönünden histopatolojiye göre daha fazla yardımcıdır.

IPF Pathogenesis

Mutation in Telomerase Reverse Transcriptase (TERT) has been implicated for the pathogenesis.

Stem/progenitor cell replace the injured and apoptotic cells in the tissue .

Mesenchymal cells in the lung and alveolar type II cells express telomerase. This enzyme plays a critical role in the enhancement of the telomerase length.

When the telomerase shortens the renewal capacity of the stem cell decreases and the cell gets aged

Presence of mutant telomerase in the parenchymal cells could be responsible for the cellular death and/or limited regeneration capacity.

Short telomerase phenotype could be found in IPF. However, telomerase length and telomerase action could be

specific to the cell and autonomous

ILD (DPLD) Diagnosis

History 1-Natural history/chronology of the disease, -acute, chronic and episodic (Eosinophilic pneumonia, vasculitides, HP or COP) 2-Respiratory risk factors and aetiological agents -Sigara -RB/ILD, DIP, LCH, Goodpasture synd., IPF (odds ratio 1.6-2.9) –HP and Sarcoidosis less likely -Occupation -Hobbies, Environment, Travel –Antigens for HP, Eosinophilic lung disease -Family History -IPF, Sarcoidosis -HIV Risk Factors -Opportunistic infections, LIP - Rheumatological Symtoms -Past Medical Hystory –Previous Malignancy, CT, RT, Surgery, -Vasculitis -Drug Hystory Symptoms -Cough, Sarcoidosis, HP, COP, IIPs,

-Wheezing, Eosinophilic pneumonia, Churg-Strauss syndrome, -Pleural Inflamation, CVDs, Asbestos exposure,Drugs, Physical Examination -Digital Clubbing, IPF, HP, CVD/ILD -Crackles (velcro) IPF, HP, Sarcoidosis -Inspiratory Squeaks, HP, NSIP, -Disease severity and cardiopulmonary capacity -Extrapulmonary Signs

DPLD (ILD) Sınıflandırması Known Cause

-Hypersensitivity pneumonitis, -Connective Tissue Diseases associated ILDs, -Drug-induced ILDs, -Smoking-related ILDs

Pulmonary Langerhans cell histiocytosis?,

Respiratory bronchiolitis-associated ILD? (RB-ILD),

Desquamative interstitial pneumonia? (DIP),

Acute eosinophilic pneumonia, -Radiation-induced ILDs, -Toxic inhalation-induced ILDs

Unknown Cause

Idiopathic Interstitial Pneumonias

-Idiopathic pulmonary fibrosis

-Non-Specific interstitial pneumonia

-Acute interstitial pneumonia

-Lymphocytic interstitial pneumonia

-RB-ILD,

-DIP,

-Cryptogenic organizing pneumonia

Eosinophilic Pneumonias

Pulmonary Lymphangioleiomyomatosis

ILD Klinik Karakteristikleri ÖYKÜ

1-Hastalığın doğal ve kronolojik seyri –akut, -kronik, -epizodik (Eozinofilik pnomoni, -vaskülit/pulmoner hemoraji, -HP, -COP 2-Risk Faktörleri, Etyolojik Nedenler -Sigara RB-ILD, DIP, LCH, Goodpasture Send., IPF(odds ratio 1.6-2.9) -HP ve Sarkoidozis zayıf olasılık, -Meslek, -Hobiler/çevre/seyahat -HP antijeni, Eozinofilik hastalık -Aile Hikayesi IPF ve Sarkoidozis, -HIV Risk Faktörü, -Opurtunistik infeksiyon , LIP, -Romatolojik Belirtiler, -Önceki Tibbi Öykü, -Malignite, KT, RT, Cerrahi girişim, Vaskülit/Hemoraji, -İlaç Tedavileri,

BELİRTİLER -Öksürük, -Sarkoidozis, HP, COP, IIP’ler, -Hışıltılı >Soluk, -Eozinofilik pnomoni, Churg –Strauss sendromu, -Hemotezi, -Wegener’s granülomatozu, Goodpasture send. -Plörezi, -KVH’lar, Asbestoz teması, İlaçlar,

FİZİK MUAYENE -Çomak parmak, -IPF, RK.HP, KVH/ILD, -Velcro benzeri crackles, -IPf, HP, Sarkoidozis, -İnspiratuar Squeaks, -HP, NSIP, -Hastalığın Şiddeti, Efor kapasitesi, -Solunum Fonksiyonları, Genelde restriktif bozukluk, Küçük hava yolları için FEF25-75 , FEF75,, FEF85

ve FVC ( FVC < % 60 ileri evre), Tlco < % 40 ileri evre hastalık

Shigeki Misumi and David A. Lynch Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia Imaging Diagnosis, Spectrum of Abnormalities, and

Temporal Progression Proc Am Thorac Soc 2006;3:307–314

Features Helpful in CT Diagnosis of Fibrotic Lung Diseases______________________________UIP______DIP_____NSIP____Kr_HP_____Subpleural predominance ++ ++ 0 ± Peribronchovascular predominance 0 0 +++ 0 Ground glass 0 +++ +++ +++ Reticular 0 0 0 0 Honeycombing ++ 0 0 0 Nodules 0 0 0 +++ Mosaic attenuation/air trapping 0 0 0 +++ Cysts 0 +++ 0 0

0 = feature is not helpful in the CT diagnosis, +++ = feature is very importante CT Diag.

Shigeki Misumi and David A. Lynch Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia Imaging Diagnosis, Spectrum of Abnormalities, and

Temporal Progression Proc Am Thorac Soc 2006;3:307–314

Prevalance of Imaging Features in Fibrotic Lung Diseases

__________________________________UIP_______DIP______NSIP_____Kr_HP____

Subpleural predominance ++ ++ 0 ±

Peribronchovascular predominance 0 0 +++ 0

Ground glass ± +++ +++ +++

Reticular +++ +++ +++ +++

Honeycombing ++ ± ± ±

Nodules 0 0 0 ++

Mosaic attenuation/air trapping 0 0 0 +++

Cysts 0 ++ 0 0

0 = feature does not occur, +++ = feature is present in all or almost all cases

Ryu JH, et al. Diagnosis of Interstitial Lung DiseasesRyu JH, et al. Diagnosis of Interstitial Lung DiseasesMayo Clin Proc Mayo Clin Proc 2007; 82;976- 2007; 82;976-986986

• Diagnosis of Interstitial Lung DiseasesDiagnosis of Interstitial Lung Diseases• Radyolojik BulgularRadyolojik Bulgular• Konsolidasyon; Konsolidasyon; • Akut: DAH, AIP, Akut Eoz.Pnomoni, COPAkut: DAH, AIP, Akut Eoz.Pnomoni, COP, , İlaçlarla ILD,İlaçlarla ILD,• Kronik: Kr. Eoz.Pnom. COP, PAP, Sarcoidosis, LenfomaKronik: Kr. Eoz.Pnom. COP, PAP, Sarcoidosis, Lenfoma• Retiküler Patern;Retiküler Patern;• Akut: Pulm. ÖdemAkut: Pulm. Ödem• Kronik: IPF, HP, Asbestozis, Sarkoidozis, İlaçlarla ILD Kronik: IPF, HP, Asbestozis, Sarkoidozis, İlaçlarla ILD • Nodüler Patern <1cm / çapNodüler Patern <1cm / çap• Akut: HP, Sarkoidozis, İnfeksiyon Akut: HP, Sarkoidozis, İnfeksiyon • Kronik: Sarkoidozis, HP, Resp. Bronşiyolitis, Alveolar Mikrolitiyazis.Kronik: Sarkoidozis, HP, Resp. Bronşiyolitis, Alveolar Mikrolitiyazis.• Kistik Kistik • Akut: Pnomosistitis pnomonisi, Septik embolizmAkut: Pnomosistitis pnomonisi, Septik embolizm• Kronik: LCH, LAM, Lenfositik interstisyel pnomoni, Bal peteği-IPFKronik: LCH, LAM, Lenfositik interstisyel pnomoni, Bal peteği-IPF• Buzlu Cam OpasiteleriBuzlu Cam Opasiteleri• Akut: DAH, HP, AIP, İlaçlara bağlı ILD,Akut: DAH, HP, AIP, İlaçlara bağlı ILD,• Kronik: NSIP, HP, Resp. Bronşiyolitis ve ILD, DIP, PAP, İlaçlara bağlı ILDKronik: NSIP, HP, Resp. Bronşiyolitis ve ILD, DIP, PAP, İlaçlara bağlı ILD

ILD (DPLD) Tanısı

Pulmonary Function Tests

-Spirometry, Diffusion capacity, oximetry,

- Arterial blood gas and pH

-Cardiopulmonary exercise test, Laboratory Tests

-Complete blood cell count

-Chemistry panel,

-Serologic tests fo HP,

-Tests for CVD,

-Antineutrophil cytoplasmic antibodies,

-BNP, proBNP, Imaging Studies

-CXR,

-Previous imaging studies,

-Chest CT and HRCT Bronchoscopy

Ryu JH, et al. Diagnosis of Interstitial Lung DiseasesRyu JH, et al. Diagnosis of Interstitial Lung DiseasesMayo Clin Proc Mayo Clin Proc 2007; 2007; 82;976-98682;976-986

Thickened Interlobular Septa -Acute: Congestive heart failure, Pulmonary edema, -Chronic: Sarkoidosis, PAP Associated FindingsAssociated Findings Traction Bronchiectasis: IPF, Asbestosis, Other chr. Fibrotic disorders,Traction Bronchiectasis: IPF, Asbestosis, Other chr. Fibrotic disorders, Lymphadenopathy: Sarkoidosis, Berilliosis, Infections, Lymphangitis cars. Lymphadenopathy: Sarkoidosis, Berilliosis, Infections, Lymphangitis cars.

Lymphoma, Lymphoma, Air Trapping: HP, Resp. Bronchiolitis associated ILD, DIP, Sarkoidosis,Air Trapping: HP, Resp. Bronchiolitis associated ILD, DIP, Sarkoidosis, Pleural Effusion or Thickening: Asbestosis, KVH-ILD, LAM, Lymphoma, Pleural Effusion or Thickening: Asbestosis, KVH-ILD, LAM, Lymphoma,

Lymnfangitic carcinomatosis, drug-induced ILDLymnfangitic carcinomatosis, drug-induced ILD ILD’nin bilinen histopatolojik patern sayısı sınırlıdır. Bu paternlerin tanısal ILD’nin bilinen histopatolojik patern sayısı sınırlıdır. Bu paternlerin tanısal

özellikleri farklıdır. Bazı biyopsi spesmenler tanısal özellikler taşırken bazıları özellikleri farklıdır. Bazı biyopsi spesmenler tanısal özellikler taşırken bazıları nonspesifik anormallikler gösterir.nonspesifik anormallikler gösterir.

Ryu JH, et al. Diagnosis of Interstitial Lung DiseasesRyu JH, et al. Diagnosis of Interstitial Lung DiseasesMayo Clin Proc Mayo Clin Proc 2007; 2007; 82;976-98682;976-986

İnterlobüler Septal Kalınlaşma -Akut: Kalp yetmezliği, Pulmoner ödem, -Kronik: Sarkoidozis, PAP Diğer BulgularDiğer Bulgular Traksiyon Bronşiyektazisi: IPF, Asbestozis, Diğer kr. Fibrotik bozukluklar,Traksiyon Bronşiyektazisi: IPF, Asbestozis, Diğer kr. Fibrotik bozukluklar, Lenfadenomegali: Sarkoidozis, Berilyozis, Silikozis, İnfeksiyon, Lenfanjitis kars. Lenfadenomegali: Sarkoidozis, Berilyozis, Silikozis, İnfeksiyon, Lenfanjitis kars.

Lenfoma, Lenfoma, Air Trapping: HP, Resp. Bronşiyolitis ve ILD, DIP, Sarkoidozis,Air Trapping: HP, Resp. Bronşiyolitis ve ILD, DIP, Sarkoidozis, Plevral Sıvı veya Kalınlaşma: Asbestozis, KVH-ILD, LAM, Lenfoma, Lenfanjitis, Plevral Sıvı veya Kalınlaşma: Asbestozis, KVH-ILD, LAM, Lenfoma, Lenfanjitis,

İlaca bağlı ILDİlaca bağlı ILD ILD’nin bilinen histopatolojik patern sayısı sınırlıdır. Bu paternlerin tanısal ILD’nin bilinen histopatolojik patern sayısı sınırlıdır. Bu paternlerin tanısal

özellikleri farklıdır. Bazı biyopsi spesmenler tanısal özellikler taşırken bazıları özellikleri farklıdır. Bazı biyopsi spesmenler tanısal özellikler taşırken bazıları nonspesifik anormallikler gösterir.nonspesifik anormallikler gösterir.

Ryu JH, et al. Diagnosis of Interstitial Lung DiseasesRyu JH, et al. Diagnosis of Interstitial Lung DiseasesMayo Clin Proc Mayo Clin Proc 2007; 82;976- 2007; 82;976-986986

• Diagnosis of Interstitial Lung DiseasesDiagnosis of Interstitial Lung Diseases• Radiologic FindingsRadiologic Findings• Consolidation; Consolidation; • Acute: DAH, AIP, Acute Eos.Pneumonia, COPAcute: DAH, AIP, Acute Eos.Pneumonia, COP , Drug-induced, Drug-induced ILD, ILD,• Chronic: Chr. Eos.Pneum. COP, PAP, Sarcoidosis, LymphomaChronic: Chr. Eos.Pneum. COP, PAP, Sarcoidosis, Lymphoma• Reticular Pattern;Reticular Pattern;• Acute: Pulm. Odema,Acute: Pulm. Odema,• Chronic: IPF, CVD/ILD, Asbestosis, Sarcoidosis, HP, İlaca bağlı ILD,Chronic: IPF, CVD/ILD, Asbestosis, Sarcoidosis, HP, İlaca bağlı ILD,• • Cystic Airspace Cystic Airspace • Acute: Pneumocystis pneumonia, Septic embolismAcute: Pneumocystis pneumonia, Septic embolism• Chronic: LCH, LAM, LIP, IPF-honeycomb lungChronic: LCH, LAM, LIP, IPF-honeycomb lung• Ground-glass OpacitiesGround-glass Opacities• Acute: DAH, HP, AIP, Drug-induced ILD,Acute: DAH, HP, AIP, Drug-induced ILD,• Chronic: NSIP, HP, Resp. Bronchiolitis associated ILD, DIP, PAP, Drug induced ILDChronic: NSIP, HP, Resp. Bronchiolitis associated ILD, DIP, PAP, Drug induced ILD

Lleslie KO. Clin Chest Med2004;25:657-703, Verbeken EK. Eur Respir J 2001;32Suppl.:107S-113SLleslie KO. Clin Chest Med2004;25:657-703, Verbeken EK. Eur Respir J 2001;32Suppl.:107S-113S

Diğer BulgularDiğer Bulgular Traksiyon Bronşiyektazisi: IPF, Asbestozis, Diğer kr. Fibrotik bozukluklar,Traksiyon Bronşiyektazisi: IPF, Asbestozis, Diğer kr. Fibrotik bozukluklar, Lenfadenomegali: Sarkoidozis, Berilyozis, Silikozis, İnfeksiyon, Lenfanjitis kars. Lenfadenomegali: Sarkoidozis, Berilyozis, Silikozis, İnfeksiyon, Lenfanjitis kars.

Lenfoma, Lenfoma, Air Trapping: HP, Resp. Bronşiyolitis ve ILD, DIP, Sarkoidozis,Air Trapping: HP, Resp. Bronşiyolitis ve ILD, DIP, Sarkoidozis, Plevral Sıvı veya Kalınlaşma: AsbestozisILD’nin bilinen histopatolojik patern sayısı Plevral Sıvı veya Kalınlaşma: AsbestozisILD’nin bilinen histopatolojik patern sayısı

sınırlıdır. Bu paternlerin tanısal özellikleri farklıdır. Bazı biyopsi spesmenler tanısal sınırlıdır. Bu paternlerin tanısal özellikleri farklıdır. Bazı biyopsi spesmenler tanısal özellikler taşırken bazıları nonspesifik anormallikler gösterir.özellikler taşırken bazıları nonspesifik anormallikler gösterir.

, KVH-ILD, LAM, Lenfoma, Lenfanjitis, İlaca bağlı ILD, KVH-ILD, LAM, Lenfoma, Lenfanjitis, İlaca bağlı ILD

Athol U. Wells1 and Cory M. Hogaboam. Update in Diffuse Parenchymal Lung Disease 2007 Am J Respir Crit Care Med 2008;Vol 177. pp 580–584,

NSIP initially was regarded as a confusing preliminary diagnosis and a presentation. It was classified as idiopathic NSIP and HP, and NSIP secondary to drug induced lung disease and especially to CVD

Recent information suggest that this distinction is not valid. When idiopathic NSIP is investigated precisely it is revealed that the clinical and serological abnormalities are due to the underlying CVD or its development, which did was not noticed. Another supporting evidence is the similarity of the survival between idiopathic NSIP and NSIP secondary to CVD. In contrast to that mortality in IPF is higher than that associated with CVD and UIP.

The classification has to be updated according to these views. The previous classification carries difficulties for the invesigations of new treatments. Fibrotic NSIP develops in HP, and is also a subgroup of idiopathic NSIP related to HP. The prognostic value of this pattern of HP is not well known, however recent data suggests that widespread reticular findings with or without honey combing and traction bronchiectasis in the CT illustrates the presence of fibrotic disease.

Athol U. Wells1 and Cory M. Hogaboam. Update in Diffuse Parenchymal Lung Disease 2007 Am J Respir Crit Care Med 2008;Vol 177. pp 580–584,

NSIP başlangıçta bir ön tanı ve tanı kargaşası yaratan tablo şeklindeydi. İdyopatik NSIP ve HP, İlaca bağlı akciğer hastalığı ve özellikle KVH’lara sekonder NSIP olarak sınıflandırılmaktaydı.

Son bilgiler bu ayrımın yapay olduğunu düşündürmektedir. İdyopatik NSIP dikkatli araştırıldığında klinik ve serolojik anormalliklerin kuvvetle altta ayrımı yapılmamış KVH’lığı veya ona doğru gidişi düşündürdüğü görülmektedir. Bunu destekleyen bir durum, idyopatik NSIP’le KVH’lara segonder NSIP survivalları benzerdir. Zıt olarak IPF’de mortalite, KVH ve UIP birlikte bulunanlardan daha yüksektir.

Bu görüşlerle yeniden sınıflandırmalıdır. Eski sınıflandırma yeni tedavi araştırmaları için zorluklar taşımaktadır. HP’de fibrotik NSIP ve UIP gelişir, ve gene çalışmaları HP’in altında idyopatik NSIP’in bir alt grubudur. HP’deki bu paternin göreceli prognostik değeri bilinmemektedir, ancak son raporlara göre BT’deki yaygın retiküler bulgular bal peteği ve traksiyon bronşiyektazisi olsun olmasın altta bulunan fibrotik hastalığı göstermektedir.