5 Varone - La diagnosi Clinica presentazione linee guida Milano … · 2020-02-07 · , µ z ] v }...

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Transcript of 5 Varone - La diagnosi Clinica presentazione linee guida Milano … · 2020-02-07 · , µ z ] v }...

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La Diagnosi ClinicaFrancesco VaroneUOC PneumologiaFondazione Policlinico A. Gemelli IRCCS Roma

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Classification of interstitial lung disease

Athol U. Wells Eur Respir Rev 2013;22:158-162

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feb. ’20 4

Athol U. Wells et al. EurRespir J 2018;51:1800692

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IPF is a specific form of chronic,progressive, fibrosing interstitialpneumonia of unknown cause.

It occurs primarily in older adults, islimited to the lungs, and is definedby the histopathologic and/orradiologic pattern of UIP

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William Osler‘‘Cirrhosis of the Lung’’

Hamman and Rich«Acute diffuse

interstitial fibrosis of the lung»

Liebow and CarringtonUsual InterstitialPneumonia (UIP)

Bronchiolitis interstitialpneumonia

Desquamative interstitialpneumonia (DIP)

Lymphoid interstitialpneumonia (LIP)

giant cell interstitialpneumonia (GIP)

Katzenstein, MyersUIP, NSIP, DIP, RB-

ILD, AIP

IPF clinical-radiological-pathologicalcorrelations

1892 1944 1969 1998 2011-present

Collard HR, King TE; Arch Intern Med. 2003 Jan 13;163(1):17-29.

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• Dense fibrosis with architecturaldistortion (i.e., destructivescarring and/or honeycombing)

• Predominant subpleural and/or paraseptal distribution of fibrosis

• Patchy involvement of lungparenchyma by fibrosis

• Fibroblast foci

• Absence of features to suggestan alternate diagnosis

Pulmonary Fibrosis and the Many Faces of UIP Springer-Verlag London 2015Raghu G et al. Am J Respir Crit Care Med 2018;198:e44–e68

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Raghu G et al. Am J Respir CritCare Med 2018;198:e44–e68

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Diagnostic workup

S. Tomassetti et al; Eur Respir Rev 2015; 24: 69–77cc

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Anamnesis

• Age• Sex• Smoking History• Onset of Symptoms (Cough, Dyspnea, etc.)• Other Symptoms (Fever, weight loss, Myalgias, etc)• Comorbidities (GERD, Diabetes, Cardiovascular, etc)• Family History• Exposures• Pets• Drugs

“A thorough and comprehensive history may provide invaluable information that can suggest certain entities and provide suspicion that a patient may have a specific diagnosis”

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Hutchinson J et al, Eur Resp J 2015; 46: 795-806

Worldwide IncidenceEpidemiology

incidence ranging from 2–30 cases per 100,000 person/yearsPrevalence ranging from 10–60 cases per 100,000 people. Population prevalence of 130,000 in the UnitedStates, 300,000 in Europe, 640,000 in East Asia and ~3 million people worldwide

In patients >65 years, the estimated prevalence of IPF is as high as 400 cases per 100,000 people

Martinez, F. J. et al. (2017) Nat. Rev. Dis. PrimersSlide Courtesy Prof. L. Richeldi

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Raghu G, et al. Am J Respir Crit Care Med. 2006;174(7):810–816

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I pazienti con IPF nella Regione Lazio

Aumento nel numero di pazienti presi in carico in ogni anno dai centri IPF

o Si è passati dagli 81 pazienti del 2014 ai 344 nel 2018, con un tasso di incremento annuo medio del 44%.

o Gli incrementi maggiori nel numero annuo di pazienti presi in carico si sono avuti negli ultimi due anni (2017-2018).

o Anche analizzando il tasso di incidenza (pazienti presi in carico/popolazione residente con età ≥ 45 anni) emerge un trend crescente.

Varone F et al Poster AIPO 2019

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I pazienti con IPF nella Regione Lazio

o La quota parte di over 75 anni tende a crescerenegli anni (30.9% del 2014 vs. 50.1% dei casi nel2018).

o In pochi casi i pazienti con diagnosi di IPF hannoun’età inferiore ai 45 anni (max annuo 1.2%, 0.3%nel 2018).

o Negli anni considerati emerge un aumento deltasso di incidenza (per 100.000 residente) per lefasce di età ≥ 65 anni.

Aumento nel numero di pazienti presi in carico con età > 65 anni

Varone F et al Poster AIPO 2019

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Data from 97 patientswith biopsy-proven IPF and 38 patients with other IIPs

Am J Respir Crit Care Med. 2010;181(8):832–837

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The Aging Lung

Thannickal VJ et al, AJRCCM, Volume 191 Number 3 February 1 2015

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Am J Respir Crit Care Med. 1997;155(1):242–248.

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Behr J et al, Eur Respir J. 2015 Jul;46(1):186-96.

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KC Meyer Translational Respiratory Medicine 2014, 2:4

Onset of Symptoms

ACUTE• AIP• Acute HP, Acute EP• Drug Reaction• COP• CTD (e.g acute lupus capillaritis)• DAH

CHRONIC• IPF• NSIP• CTD-ILD• CHP• CEP• Sarcoidosis

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Am J Respir Crit Care Med. 2016 Aug 1;194(3):265-75. doi: 10.1164/rccm.201604-0801CI

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Comorbidities

King CS, Nathan SD, Lancet Resp Med ,2016 doi.org/10.1016/S2213-

2600(16)30222-3

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Comorbidities

Kreuter M, et al PLOS ONE | DOI:10.1371/journal.pone.0151425 March 29, 2016

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S. Tomassetti et al, Chest 2015; 147(1):157-164

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Exposures

Metal dusts

Wood dusts

Silica

Asbestos

Fungal, bacterial, protozoal, and animal proteins

Molds

Isocyanates found in paints, foams, and sealants

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Vasakova M, et al. Am J Respir Crit Care Med. 2019 May 31

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142 consecutive adult patients

Chest. 2013 Nov;144(5):1644-1651

Adju

sted

for

mea

n ag

e 55

ys

Adju

sted

for

mea

n ag

e 60

ys

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García-Sancho C, et al Respir Med. 2011;105(12):1902–1907.

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Genome Wide Association Study in IIP

Chromosome

-lo

g1

0(P

val

ue

)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 2122 X

5

10

15

20

TERC

MUC5B

TERT

FAM13A

DPP9ATP11A

OBFC1

DSP30-33% of

the disease risk

Fingerlin. Nat Genet 2013; 45:613

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Mathai et al, BMC Med 2015; 13: 191

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Telomeropathy

TERT TERC RTEL1

PARN

Newton CA, et al. Eur Respir J. 2016;48(6):1710–1720

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Adegunsoye A, et al. Chest. 2019;155(5):1026–1040

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Drugs

Kubo K, et al. Respiratory investigation 51 (2013) 260–277

Schwaiblmair M et al, The Open Respiratory Medicine Journal, 2012, 6, 63-74

www.pneumotox.com

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HP

OP

NSIP

UIP

Kubo K, et al. Respiratory investigation 51 (2013) 260–277

Schwaiblmair M et al, The Open Respiratory Medicine Journal, 2012, 6, 63-74

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Physical Examination• No specific sign for IPF • Velcro crackles• Clubbing• Cianosis

Behr J et al, Eur Respir J. 2015 Jul;46(1):186-96.

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KC Meyer Translational Respiratory Medicine 2014, 2:4

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Serological testing for excluding connective tissue disease

ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis 1. Raghu G et al. Am J Respir Crit Care Med 2018;198:e44–e68; 2. Raghu G et al. Am J Respir Crit Care Med 2011;183:788–824; 3. Lynch DA et al. Lancet Respir Med 2018;6:138–153

2018 guidelines1

Recommendation Serological testing to exclude connective tissue diseases as a potential cause of ILD

RationaleExclusion of other causes of ILD, including connective tissue disease-ILD are mandatory for a diagnosis of IPF and routine serological testing is the best way to do this

Diagnosis of IPF requires exclusion of other known causes of ILD (eg domestic and occupational environmental exposures, connective tissue disease, and drug toxicity)

2011 guidelines2

A systematic assessment for connective tissue disease is necessary for an IPF diagnosis. Serological findings can suggest an autoimmune disorder eg mixed-connective tissue disease

FleischnerSociety3

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Connective Tissue Disease Associated Interstitial Lung Disease

Connective Tissue Disease Type of ILD Estimated Prevalence of ILD CTD is Occult

Dermatomyositis Polymyositis

Anti-synthetase syndrome

NSIP with OP NSIP OP UIP

40% Often

Sjogren’s syndromeNSIP UIP LIP

Up to 40% Less often

Systemic sclerosis NSIP UIP

50% (80% subclinical) Less often

Rheumatoid arthritisUIP

NSIPOP

50% (80% subclinical) Less often

Interstitial pneumonia with autoimmune features

NSIP OP

NSIP/OP UIP

10% (30% subclinical) Often

CTD: Connective tissue disease; ILD: Interstitial lung disease; LIP: Lymphocytic interstitial pneumonia; OP: Organizing pneumonia; UIP: Usualinterstitial pneumonia.

Raghu G et al. Am J Respir Crit Care Med 2018;198:e44–e68; 2

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Eur Respir J 2010; 35: 1322–1328

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RA-UIP

IPF

RA-NOT UIP

RA-UIP

RA-LIKELY NSIP

INDETERMINATE

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Connective Tissue Disease Associated Interstitial Lung Disease

Connective TissueDisease

Laboratory Workup

All Patients with newly identified ILD

CRP (C-reactive protein), erythrocyte sedimentationrate, antinuclear antibodies (by immunofluorescence), rheumatoid factor,

myositis panel, and anti–cyclic citrullinated peptide

Suspected Myositis CPK, myoglobin, aldolase, antisynthetase antibodies (Jo-1 and others ifavailable), anti–MDA5, anti– Mi-2, anti-NXP2), anti–TIF1-g, anti-SRP, anti-

HMGCR, anti-SAE, anti-U1RNP, anti-PM/Scl75, anti-PM/ Scl100, and anti-Ku

Suspected Systemicsclerosis

anti–Scl-70/topoisomerase-1, anti-centromere, anti-RNA polymerase III, anti-U1RNP, anti-Th/To, anti-PMScl, U3 RNP (fibrillarin), and anti-Ku

Suspected Sjogren’ssyndrome

anti-SSA/Ro (Sjogren-specific antibody A) and anti-SSB/La

Suspected Vasculitis anti- cytoplasmic antibodies

Raghu G et al. Am J Respir Crit Care Med 2018;198:e44–e68; 2

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Rheumatologic Evaluation

Fischer/Lee/Cottin Respiration 2015;90:177–184 DOI: 10.1159/000440665

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DYNAMIC

INTEGRATED

APPROACH

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Flaherty KR, et al AJRCCM. 2004;170(8):904–910

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Lancet Respir Med. 2016 Jul;4(7):557-65.

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TIME

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Conclusions• IPF diagnosis should be considered in all adult patients with unexplained

chronic exertional dyspnea, cough, bibasilar inspiratory crackles, and/or digital clubbing that occur without constitutional or other symptomsthat suggest a multisystem disease

• Clinical context is fundamental (age>60 ys, male predominant, smoking history frequent)

• No specific sign and/or symptoms

• Misdiagnosis is frequent

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