Pascal Van Bleyenbergh, Pneumologie UZ Leuven · 2016-03-07 · 7/03/2016 1 The clinicalspectrum of...

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The clinical spectrum of pulmonary aspergillosis

Pascal Van Bleyenbergh, Pneumologie UZ Leuven

Pentalfa 3 maart 2016

Aspergillus species• First described in 1729 * >250 species * ubiquitous

• Inhalation of conidia common * only minority lung disease

• Most common cause of mortality due to invasive mycosis

• Variety of clinical syndromes

Latge JP. Clin Microbiol Rev 1999; 12: 310-350

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Broad Spectrum of Pulmonary Aspergillosis

Kosmidis C, Denning DW. Thorax 2015; 70(3): 270-277

SAFS

Broad Spectrum of Pulmonary Aspergillosis

Hope WW et al. Med Mycol 2005; 43(Suppl 1): 207–38

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Chronic pulmonary aspergillosis (CPA)

Chronic pulmonary aspergillosis (CPA)

- 1842: ‘parasitic vegetable structures’ (Bennett J)- 1938: ‘mega-mycetoma intra-bronchiectasique’ (Deve F)- 1957: amphotericine B for treating chronic aspergillosis complicating TB

(Kelmenson VA)- 1981: ‘semi-invasive pulmonary aspergillosis’ (Gefter WB et al.)- 1982: ‘chronic necrotizing pulmonary aspergillosis’ (Binder RE et al.)

Gefter WB et al. Radiology 1981; 140: 313-321Binder RE et al. Medicine 1982; 61: 109-124

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Chronic Pulmonary Aspergillosis (CPA)

Denning DW et al. Eur Resp J 2016; 47: 45-68

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Simple (single) aspergilloma• Fungal ball (= hyphae and extracellular matrix)

• Pre-existing cavity: lung, pleura, ectatic bronchus

• Characteristic imaging features (RX / CT)

• Serological or microbiological evidence implicating Aspergillus

• No progression over 3 months

• No or very few pulmonary/systemic symptoms

• Non-immunocompromised patient


Simple (single) aspergilloma


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Aspergillus nodule• One or more nodules

• <3cm,only rarely >3cm (with necrotic centre)

• Usually no cavitation

• No tissue invasion

• Unusual presentation of CPA…

• Broad differential diagnosis (lung carcinoma, metastases, other fungal infection, ...)


Aspergillus nodule


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Chronic cavitary pulmonary aspergillosis (CCPA)

• Multiple cavities +/- fungal ball

• Radiological progression over 3 months(new cavities, increasing infiltrates, increasing fibrosis)

• Significant pulmonary/systemic symptoms


• CFPA (chronic fibrosing pulmonary aspergillosis) is end result of CCPA with extensive fibrotic destruction of at least two lobes!

= most frequent presentation of CPA!

Denning DW et al. Clin Infect Dis 2003; 37(Suppl3): 265-280



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Subacute invasive pulmonary aspergillosis (SAIA)

• ‘chronic necrotizing’ or ‘semi-invasive’ pulmonary aspergillosis

• Clinically and radiologically similar to CCPA but more rapid in progression (<<3 months)

• Mildly immunocompromised patient / structural lung disease(diabetes, malnutrition, alcoholism, advanced age, prolonged corticosteroidtherapy, COPD, connective tissue disorder, radiation therapy, NTM disease, HIV,…)


• Signs of invasive disease possible (hyphae in lung tissue)


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Chronic pulmonary aspergillosis – diagnostic criteria



1.1 Characteristic CT appearance of a fungus ball in a pulmonary or pleural cavity, or dilated bronchus


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1.1 Characteristic CT appearance of a fungus ball in a pulmonary or pleural cavity, or dilated bronchusOR1.2 Radiological features consistent with chronic pulmonary aspergillosis (cavities, pleural thickening, extensive fibrosis, nodules,…)




AND2. Clinical or radiological evidence of at least 3 months disease (shorter duration possible for SAIA)


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AND2. Clinical or radiological evidence of at least 3 months disease (shorter duration possible for SAIA)

AND3. Histological or microbiological or immunological evidence of Aspergillusinfection (hyphae in biopsy or Asp. culture in cavity aspiration, strongly positive BAL GM, positive IgG/precipitins). Respiratory tract cultures or PCR positive for Aspergillus is supportive.


Histological or microbiological or immunological evidence of Aspergillus infection

Biopsy or resection of lesions: definitive distinction between SAIA and CCPA

Presence of Aspergillus in respiratory secretions (stain, cultures, PCR)- supportive but not diagnostic- suboptimal sensitivity (56%-81%)- culture: media specific for fungi- PCR more sensitive than culture- persistance during antifungal therapy resistance!

Galactomannan- BAL >> serum- much higher sensitivity and specificity (85,7% & 77%)

Aspergillus antibodies (IgG, precipitins – no role of IgA & IgM)- key diagnostic feature in CPA- antibody titers no correlation with extent of severity of disease (…)


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Chronic pulmonary aspergillosis – diagnostic criteria1.1 Characteristic CT appearance of a fungus ball in a pulmonary or pleural cavity, or dilated bronchus1.2 Radiological features consistent with chronic pulmonary aspergillosis

2. Clinical or radiological evidence of at least 3 months disease

3. Histological or microbiological or immunological evidence of Aspergillus infection

AND

Exclusion of

- active bacterial infection, including mycobacterial infection

- actinomycosis

- histoplasmosis and (para)coccidioidomycosis in endemic areas

- malignancies, vasculitides, rheumatoid nodules,…


Diagnosis of SAIA= diagnosis of IPA in the immunocompromised host (EORTC)

De Pauw B et al. Clin Infect Dis 2008; 46: 1813-1821

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Diagnosis of SAIA= diagnosis of IPA in the immunocompromised host (EORTC)

Bulpa P et al. Eur Resp J 2007; 30: 782-800

4) Positive BAL galactomannan test

Underlying conditions in pts with CPA

Smith NL et al. Eur Respir J 2011; 37: 865-872Godet C et al. Resp 2014; 88: 162-174

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CPA in patients with COPD

Guinea J et al. Clin Microbiol Infect 2010; 16: 870-877

2000-200714.618 COPD admissions

16,3 Asp.+/1000 admissions53 ‘probable’ PA➜ 3,6/1000 admissions➜ 22,1% if Asp.+

CPA in patients with NTM disease

• 11% of NTM patients (3,9% - 16,7%)

• CCPA >> CNPA (89% vs 11%)

• Cavitary NTM disease

• Prior use of corticosteroids

• Poorer prognosis

• Interactions with azoles!➪ CPA >> NTM treatment

Kunst H et al. Eur Resp J 2006; 28: 352-357Kazuaki T et al. Med Myc 2016; 54: 120-127

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Therapy for CPA• Cohort studies and case reports; only 2 larger prospective studies

• Aspergilloma: surgery is first choice!

• Oral azole therapy for CCPA is standard of care!➜ itraconazole, voriconazole, posaconazole

Agarwal R et al. Mycoses 2013; 56: 559-570Denning DW et al. Eur Resp J 2016; 47: 45-68

Therapy for CPA• Cohort studies and case reports; only 2 larger prospective studies

• Aspergilloma: surgery is first choice!

• Oral azole therapy for CCPA is standard of care!➜ itraconazole, voriconazole, posaconazole

• SAIA: treat as invasive pulmonary aspergillosis! (IDSA/ATS guidelines)

• Response to antifungal treatment is slow…

• Duration: 4-6 months 9 months12 months

• Quid indefinite long-term suppressive therapy?

Agarwal R et al. Mycoses 2013; 56: 559-570Denning DW et al. Eur Resp J 2016; 47: 45-68

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CPA: treatment needs to be “long term”


CPA: treatment needs to be “long term”

Cadranel J et al. Eur J Clin Microbiol Infect Dis 2012; 31: 3231-3239 --- Al-shair K et al. Clin Infect Dis 2013; 57: 828-835 Agarwal R et al. Mycosis 2013; 56: 559-570

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CPA:global treatment strategy

Godet C et al. Resp 2014; 88: 162-174Ohara S et al. Resp Invest 2016; 54: 92-97

• Attention for co-morbidities

smoking, alcohol intake

malnutrition

corticosteroids

• Pulmonary rehabilitation

Pascal Van Bleyenbergh, Pneumologie UZ Leuven · 2016-03-07 · 7/03/2016 1 The clinicalspectrum of...

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