Σοβαρό άσθμα και Περιφερική ηωσινοφιλία Διαχειριστικά προβλήματα Ευφροσύνη Δ. Μάναλη Β Πνευμονολογική Κλινική ΓΝΑ «Αττικόν» Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών Ιατρική Σχολή
Severe asthma is defined as asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming uncontrolled or which remains uncontrolled despite this therapy. It is increasingly evident that severe asthma is not a single disease
The treatment of severe asthma relies heavily on the maximal optimal use of corticosteroids and bronchodilators, and other controllers There is a potential for other add-on benefits of additional biological agents to providing benefit in severe asthma
Evaluation of severe asthma patient Assessment of confounding factors and comorbidities Assessment and subsequent treatment of rhino-sinusitis
Evaluation of severe asthma patient with peripheral eosinophilia Assessment of persistent eosinophilia (eosinophilia in asthma rarely exceeds 0.8 x 109 cells/l) Assessment and subsequent treatment of allergic fungal disease of the respiratory tract Assessment of multiorgan involvement
Clinicians should maintain a degree of scepticism regarding the diagnosis and establish whether the patient s history and evaluation truly represent only severe asthma with eosinophilia or another condition
Bhatt NY, et al. Semin Respir Crit Care Med 2012; 33:555-571
Senecio, Paul Klee 1922
Ασθενής άνδρας 50 ετών, μη καπνιστής
14-07-10
17.9.2010 Εμπύρετο με παραγωγικό βήχα, δύσπνοια, αίσθημα βάρους στο προκάρδιο Νοσηλεία προ 15ημέρου λόγω παρόμοιας συμπτωματολογίας, λήψη αναπνευστικής κινολόνης. Εξέρχεται με τη διάγνωση «Παρόξυνση ΒΑ σε αποδρομή» Συνιστάται CT θώρακος κατά την έξοδο Ενζυμική κίνηση Τροπονίνη =0.35ng/ml Σοβαρό Βρογχικό άσθμα με χρόνια λήψη κορτικοειδών από του στόματος. Α.Υ. Καταρράκτης άμφω. Οστεοπενία
Eosinophils 3600/μL, IgE: 4080 IU/ml Ανοσολογικός έλεγχος αρνητικός
27-9-10: ΟΙΔΗΜΑ ΣΤΟ ΒΑΣΙΚΟ ΠΛΑΓΙΟ ΤΜΗΜΑ ΤΗΣ ΑΡ ΚΟΙΛΙΑΣ - ΟΙΔΗΜΑ ΠΕΤΑΛΩΝ ΠΕΡΙΚΑΡΔΙΟΥ ΜΕ ΜΙΚΡΗ ΠΕΡΙΚΑΡΔΙΑΚΗ ΣΥΛΛΟΓΗ 27-9-10: ΑΚΟΛΟΥΘΙΑ ΒΙΩΣΙΜΟΤΗΤΟΣ. ΕΣΤΙΕΣ ΣΚΙΑΓΡΑΦΙΚΗΣ ΕΝΙΣΧΥΣΗΣ ΣΤΟ ΒΑΣΙΚΟ ΠΛΑΓΙΟ ΤΟΙΧΩΜΑ ΑΝΤΙΣΤΟΙΧΑ ΜΕ ΤΟ ΟΙΔΗΜΑ 27-09-10: ΑΚΟΛΟΥΘΙΑ ΒΙΩΣΙΜΟΤΗΤΑΣ. EΣΤΙΕΣ ΕΝΙΣΧΥΣΗΣ ΣΤΟ ΒΑΣΙΚΟ -ΜΕΣΟ ΚΑΤΩΤΕΡΟ, ΟΠΙΣΘΙΟ ΤΟΙΧΩΜΑ ΤΗΣ ΑΡ ΚΟΙΛΙΑΣ ΜΕ ΕΝΤΟΝΗ ΣΚΙΑΓΡΑΦΙΚΗ ΕΝΙΣΧΥΣΗ ΚΑΙ ΟΡΙΑΚΗ ΠΑΧΥΝΣΗ ΠΕΡΙΚΑΡΔΙΟΥ
ΣΤΕΦΑΝΙΟΓΡΑΦΙΑ ΔΕΞΙΟΣ ΚΑΙ ΑΡΙΣΤΕΡΟΣ ΚΑΘΕΤΗΡΙΑΣΜΟΣ ΦΥΣΙΟΛΟΓΙΚΑ ΣΤΕΦΑΝΙΑΙΑ ΑΓΓΕΙΑ ΑΥΞΗΜΕΝΕΣ ΔΙΑΣΤΑΣΕΙΣ ΑΡ. ΚΟΙΛΙΑΣ (Κ.Ε: 55%) ΑΠΟΥΣΙΑ MR ΦΥΣΙΟΛΟΓΙΚΕΣ ΠΙΕΣΕΙΣ ΚΟΙΛΟΤΗΤΩΝ ΒΙΟΨΙΕΣ ΔΕ ΚΟΙΛΙΑΣ
Διάγνωση: Αγγειΐτιδα Churg Strauss ΘΕΡΑΠΕΙΑ Αύξηση κορτιζόνης ΑΜΕΑ & Επλερενόνη Διλτιαζέμη & Αμιωδαρόνη Mycophenolate Mofetil
9-2-11: ΑΚΟΛΟΥΘΙΑ ΒΙΩΣΙΜΟΤΗΤΑΣ. ΚΑΤΑ ΤΟΝ ΒΡΑΧΥ ΑΞΟΝΑ ΕΠΑΝΕΛΕΓΧΕΤΑΙ ΠΕΡΙΟΧΗ ΚΑΘΥΣΤΕΡΗΜΕΝΗΣ ΣΚΙΑΓΡΑΦΙΚΗΣ ΕΝΙΣΧΥΣΗΣ ΚΑΤΑ ΤΟ ΒΑΣΙΚΟ ΠΛΑΓΙΟ ΤΟΙΧΩΜΑ ΤΗΣ ΑΡ ΚΟΙΛΙΑΣ. ΜΙΚΡΟΤΕΡΟΥ ΒΑΘΜΟΥ
2014 FEV1=81.9% Πλήρης ύφεση της περιφερικής ηωσινοφιλίας
Red Balloon, Paul Klee 1922
The estimated incidence is approximately 0.11 to 2.66 new cases per 1million people per year, with an overall prevalence of 10.7 to 14 per 1 million adults. No gender predominance or ethnic predisposition has clearly been demonstrated
Both vessel inflammation and eosinophilic proliferation are thought to contribute to organ damage, but the clinical presentations are heterogeneous Greco A, et al. Autoimmun Rev 2015; 14:341-348
The most important information that CMR can give in ANCA-associated vasculitis is the evaluation of disease acuity using the combination of oedema and fibrosis imaging. In this context, subendocardial vasculitis presents with diffuse subendocardial fibrosis, myocarditis with intramural or subepicardial lesions not following the distribution of coronary arteries and myocardial infarction with subendocardial or transmural lesions following the distribution of coronary arteries
EGPA is thought to evolve through a prodromic phase characterized by asthma, an eosinophilic phase marked by peripheral eosinophilia and organ involvement (lungs, GI, heart) and a vasculitic phase with clinical manifestations due to small-vessel vasculitis (skin, kidney, mononeuritis). Two large studies demonstrated that ANCA-positive patients had peripheral neuropathy, glomerulonephritis, and purpura (which are due to small-vessel vasculitis) more frequently compared to myocardial involvement, lung infiltrates, and gastrointestinal symptoms that prevailed in the ANCA negative subset
There are no commonly accepted diagnostic criteria for EGPA.
Active EGPA is characterized by marked peripheral eosinophilia (usually >1500 cells/μl or >10%). ANCA may arise several years before the onset of vasculitis. Antineutrophil cytoplasmic antibody-positivity needs to be confirmed by the presence of myeloperoxidase in serum. New biomarkers are emerging (eotaxin-3, an eosinophil-attracting chemokine) Biopsy of an affected organ is essential to confirm the presence of an eosinophilic inflammatory process or vasculitis. However, characteristic pathological changes need not be present to establish the diagnosis of Churg Strauss syndrome. To summarize, the diagnosis of CSA is established mainly on clinical grounds.
Prognosis If left untreated the mortality of CSS was found to be similar to that of untreated GPA at values approaching 50% at three months >30% of patients in remission relapse
Prognosis With the introduction of corticosteroid treatment, remission and survival have improved greatly. The French Vasculitis Study Group has identified five prognostic factors, the five-factor score (FFS): 1. elevated serum creatinine levels (>1.58 mg/dl) 2. proteinuria (>1 g per day), 3. gastrointestinal tract involvement 4. Cardiomyopathy and 5. central nervous system involvement. For patients without poor prognosis factors (FFS = 0), survival rates at one and five years were 100% and 97%, respectively. For patients with poor prognosis factors (FFS 1), 92% were alive at the 8-year follow-up analysis.
Patients without poor-prognosis factors are usually treated with glucocorticoids alone, whereas those with a worse prognosis are recommended glucocorticoids and immunosuppressants.
Hauptweg und Nebenwege Paul Klee 1929
Ασθενής 33 ετών μη καπνίστρια με ιστορικό αλλεργικής ρινίτιδας από την παιδική ηλικία και βρογχικό άσθμα για τα τελευταία έτη Εισάγεται στο Νοσοκομείο για παρόξυνση βρογχικού άσθματος με πυρετό Η ασθενής αναφέρει ότι τους τελευταίους μήνες πραγματοποιούνται κατασκευαστικά έργα κοντά στην κατοικία της
Laboratory, radiology and PFTs parameters Patient Bronchial asthma Central bronchiectasis on chest CT yes yes Immediate cutaneous reactivity to positive A.niger Total serum IgE Elevated serum IgE-A.niger and/or IgG-A. niger 5078 IU/ml IgG Aspergillus abs>1/2560 Aspergillus IgM abs positive Chest roentenographic infiltrates present Peripheral eosinophilia present (10.8%)
Aspergillus spp are the cause of a variety of pulmonary abnormalities that range in severity from commensal overgrowth of airways to invasion of the lung and its blood vessels, leading to sepsis and death.
Allergic bronchopulmonary aspergillosis (ABPA) represents an immunological fungal lung disease caused by type I and III hypersensitivity reactions to antigens of Aspergillus species. This clinical entity is identified in 1%-2% of patients with bronchial asthma
Katze und Vogel, Paul Klee 1928
Ασθενής γυναίκα 32 ετών, ουδέποτε καπνίστρια, αισθητικός, υπάλληλος σε κατάστημα καλλυντικών Α/α: Βρογχικό άσθμα, εποχική ρινίτιδα, ρινικοί πολύποδες, αλλεργία στην ασπιρίνη
14/04/2009 Συμπτώματα: δεκατική πυρετική κίνηση έως 37,8 ο C, αδυναμία, καταβολή χωρίς δύσπνοια
Ag Aspergillus: αρνητικά ANA: 1/640 PLTs 722.000 Ηωσινόφιλα: 13% CRP 95 TKE 100, DLCO = 60% pred 10/04/2009
Βρογχοσκόπηση: τραχειακός βρόγχος (δε), έγινε bal κυτταρολογική (-) για κακοήθεια Eosinophils: 33%
20/04/2009
11/2010
08/2011
18/02/2013
ICEP is a rare disorder One third to one half of the ICEP patients have a history of asthma Symptoms are non-specific, Dyspnea and cough are always present Extrathoracic features are absent in ICEP. When present, think of Churg-Strauss syndrome (CSS) or idiopathic hypereosinophilic syndrome (IHS) Blood eosinophilia present in most cases, usually in excess of 1000/mm3. diagnosis of ICEP is supported by the demonstration of bronchoalveolar lavage eosinophilia ( 40%). Although response to corticosteroid treatment is dramatic, relapses of ICEP are observed in up to 50% of patients
At CT, CEP is characterized by the presence of homogeneous peripheral airspace consolidation, whereas in Churg-Strauss syndrome, peripheral consolidation has a tendency toward lobular distribution and, frequently, associated centrilobular nodules within the ground-glass opacity Jeong YJ, et al. Radiographics 2007; 27: 617-639
Clinicians should maintain a degree of skepticism when evaluating and treating a patient with severe asthma and peripheral eosinophilia Long-term and meticulous follow-up of patients is desirable because the clinical features of severe asthma with peripheral eosinophilia can evolve over time
Σας ευχαριστώ πολύ Ad Parnassum, Paul Klee 1932