Le Interstiziopatie diffuse

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1 Università degli Studi di Perugia Facoltà di Medicina e Chirurgia Cattedra di Malattie dell Apparato Respiratorio Le Interstiziopatie diffuse L. Casali

2 Interstiziopatie Diffuse Gruppo di affezioni che interessano i setti interalveolari, gli alveoli, il lume e le pareti delle piccole vie aeree (dotti alveolari, bronchioli respiratori e bronchioli terminali). Già all esordio clinico vi è il coinvolgimento di più di un lobo con un attacco profondo alle unità di scambio. L elemento distintivo è rappresentato dalla proliferazione di fibroblasti e da un eccesso di deposizione di collageno sia come risposta immediata ad uno stimolo sia come risultante diun complesso processo di distruzione e riparazione.

3 A drawing of the connective tissue support of the normal human adult lung lobule demonstrates the exchange of fibers composing the elastic continuum. AD alveolar duct; ALV alveolus; IS interstitial space;pa pulmonary artery; PV pulmonary vein; RB respiratory bronchiole

4 Lobulo secondario-aspetto istologico. A dotto alveolare; P pleura; R bronchiolo respiratorio; T bronchiolo terminale

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8 Ipotesi Infiammatoria Ipotesi predominante tra il 1970 e 1980 Danno Infiammazione Fibrosi Noble PW, Homer RJ. Clin Chest Med. 2004;25: , vii. Raghu G, Chang J. Clin Chest Med. 2004;25: , v

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10 Ipotesi Remodeling Vascolare Aumentata angiogenesi Remodeling vascolare Fibrosi Alterata produzione chemochine Aumentata angiogenesi Anomalo rimodellamento vascolare Noble PW, Homer RJ. Clin Chest Med. 2004;25: , vii. Strieter RM, et al. Am J Respir Cell Mol Biol. 2003;29(3 suppl):s67-s69.

11 Schema con le condizioni che possono culminare con Fibrosi polmonare

12 Interstitial Lung Diseases and Underlying Clinical Entities Usual interstitial pneumonia (UIP) like pattern: idiopathic (UIP), collagen vascular disease (scleroderma), asbestos interstitial lung disease. Desquamative interstitial pneumonitis (DIP): idiopathic. Lymphoid interstitial pneumonitis (LIP): idiopathic, collagen vascular disease (Sjögren's disease), AIDS, immunosuppression (acquired or hereditary), viral (Epstein- Barr virus [EBV] infection). Nonspecific interstitial pneumonitis (NSIP): idiopathic; NSIP-like due to hypersensitivity pneumonitis, NSIP-like due to collagen vascular disease (i.e., scleroderma). Giant cell interstitial pneumonitis (GIP): heavy metal exposure.

13 Chronic interstitial lung patterns. A, Acute interstitial pneumonia (AIP) evolving into fibrotic stage with extensive and relatively diffuse septal thickening by fibrosis. B D, Usual interstitial pneumonia (UIP), showing its heterogeneous presentation, with areas of alveolar collapse and replacement by active fibrogenic and inflammatory process (B), with areas of honeycombing (C), and presence of fibroblastic foci (D). E G, Desquamative interstitial pneumonitis (DIP) with the characteristic uniform filling of alveolar spaces (E) with macrophages (F); once treated, DIP presents with a nonspecific type of regular interstitial thickening (arrows) (G). H, Lymphocytic interstitial pneumonitis (LIP) with dense and uniform infiltration by lymphocytes and plasma cells. I and J, Nonspecific interstitial pneumonitis (NSIP) type III with temporally homogeneous extensive fibrosis (I and J), alternating with areas with irregular interstitial inflammation (I and K; arrows in J and K highlight septal inflammation extending into intralobular septa compare with L; arrowheads highlight similar inflammatory process but with alveolar collapse in the subpleural region). L, Honeycombing with lung parenchyma replaced by cystic areas surrounded by dense fibrosis and containing mucinous material (arrows).

14 IPF: is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of UIP. Official ATS/ERS/JRS/ALAT Statement Am J Respir Crit Care Med Vol 183. pp , 2011

15 IPF is a fatal lung disease; the natural history is variable and unpredictable: a.most patients with IPF demonstrate a gradual worsening of lung function over years; a minority of patients remains stable or declines rapidly. a.some patients may experience episodes of acute respiratory worsening despite previous stability. Official ATS/ERS/JRS/ALAT Statement Am J Respir Crit Care Med Vol 183. pp , 2011

16 BEWARE OF COMORBIDITIES & RISK FACTORS smoking emphysema Pulmonary Hypertension obesity WORSE OUTCOME Right earth disfunction GERD Asymetric disease on HRCT!!!! sleeping position Microbial Agent EBV HCV

17 Disease progression is manifested by increasing respiratory symptoms, worsening pulmonary function test results, progressive fibrosis on HRCT, acute respiratory decline, or death. Official ATS/ERS/JRS/ALAT Statement Am J Respir Crit Care Med Vol 183. pp , 2011

18 Elementi prognostici predittivi Prognosi scadente: Età avanzata, sesso maschile, grado di dispnea, fumo, alterazioni funzionali, neutrofilia e/o eosinofilia al BAL, polmone a nido d ape, presenza di foci fibroblastici nei campioni bioptici.

19 Caratteristiche cliniche, radiologiche e funzionali generali delle Interstiziopatie a) Dispnea ingravescente e tosse secca b) Alterazioni radiografiche c) Prove funzionali respiratorie alterate Non sempre queste caratteristiche sono presenti: 5-10% dei pz. possono presentare una Rx normale. Pz. sintomatici possono avere prove di funzionalità respiratoria di routine entro i limiti della norma

20 IPF- Quadro clinico Sintomi principali: Dispnea ingravescente- Tosse secca Sintomi meno frequenti: Astenia, calo ponderale, malessere- Dolore toracico Segno clinico principale: Rantoli a velcro Segni aggiuntivi: Dita a bacchetta di tamburo- Cianosi

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23 Honeycombing with or without traction bronchiectasis

24 Sub pleural, basal predominance

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27 Modello di decadimento della funzione respiratoria in corso di IPF

28 Acute Exacerbations of Idiopathic Pulmonary Fibrosis Harold R. et Al. Am J Respir Crit Care Med Vol 176. pp , 2007

29 Acute Exacerbations of Idiopathic Pulmonary Fibrosis Harold R. et Al. Am J Respir Crit Care Med Vol 176. pp , 2007

30 SELECTED FEATURES ASSOCIATED WITH INCREASED RISK OF MORTALITY IN IDIOPATHIC PULMONARY FIBROSIS Official ATS/ERS/JRS/ALAT Statement Am J Respir Crit Care Med Vol 183. pp , 2011

31 Sopravvivenza in funzione della saturazione in O 2 (SaO 2 %) dopo 6 min. walk. test

32 CHEST 2011 SURVIVOR GROUP DE NOVO PATIENTS SURVIVAL

33 Scarto di sopravvivenza tra inizio dei sintomi e diagnosi

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35 When assessed by expert clinicians and radiologists, the presence of typical clinical and HRCT features is sufficient to allow a confident diagnosis of IPF in more than 50% of suspected cases and may eliminate the need for surgical lung biopsy in these patients.

36 2010 Biopsy is required only when the HRCT scan and/or the clinical features are not typical of UIP, a situation occurring in <50% of patients with IPF. However, HRCT maintains a role in determining the most appropriate site of biopsy, and the prognosis is further refined when histological data are integrated with HRCT and clinico-functional parameters.

37 C.E. anni 18 non fumatrice IRA con quadro TC torace di «micronodulia polmonare diffusa» TBB : granuloma tubercolare FBS : flogosi diffusa B.K. diretto negativo B.K. colturale : POSITIVO

38 Criteri diagnostici Diagnosi altamente probabile (spec.>95%) quando siano soddisfatti 4 criteri maggiori ed almeno 3 dei criteri minori. Criteri maggiori: -Esclusione di altre cause di interstiziopatia -Anormalità delle prove di funzionalità respiratoria (S. restrittiva e < DLCO) -Quadro HRCT caratteristico -Assenza di ipotesi alternative su campioni bioptici o su BAL Criteri minori: -Età > 50 anni -Inizio subdolo e dispnea da sforzo non altrimenti spiegabili -Durata > 3 mesi -Rantoli a velcro HRCT da solo è caratteristico nel 60-75% dei casi

39 The diagnosis of IPF requires: A.Exclusion of other known causes of interstitial lung disease (ILD) (e.g., domestic and occupational environmental exposures, connective tissue disease, and drug toxicity). B.The presence of a UIP pattern on high-resolution computed tomography (HRCT) in patients not subjected to surgical lung biopsy. C.Specific combinations of HRCT and surgical lung biopsy pattern in patients subjected to surgical lung biopsy. Official ATS/ERS/JRS/ALAT Statement Am J Respir Crit Care Med Vol 183. pp , 2011

40 The accuracy of the diagnosis of IPF Increases with multidisciplinary discussion between pulmonologists, radiologists, and pathologists experienced in the diagnosis of ILD. Official ATS/ERS/JRS/ALAT Statement Am J Respir Crit Care Med Vol 183. pp , 2011

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43 Pulmonary Hypertension and Idiopathic Pulmonary Fibrosis Farkas et al. Am J Respir Cell Mol Biol Vol 45. pp 1 15,

44 Idiopathic Pulmonary Fibrosis And Non-Specific Interstitial Pneumonia

45 Patients with IPF may have subclinical or overt comorbid conditions including pulmonary hypertension, gastroesophageal reflux, obstructive sleep apnea, obesity, and emphysema. The impact of these conditions on the outcome of patients with IPF is unclear. Official ATS/ERS/JRS/ALAT Statement Am J Respir Crit Care Med Vol 183. pp , 2011