Chronic Pulmonary Aspergillosis and Ambisome Aerosol with Itraconazole

Inclusion Criteria:

All adult patients affected with Chronic Pulmonary Aspergillosis (CPA) "de novo" or in relapse (without any history of resistance to itraconazole) combining the following criteria are eligible:

1. Patient with an Aspergillus bronchopulmonary infection, be it cavitary, fibrotic,necrotizing (SIA/Semi Invasive Aspergillosis) or nodular and documented bycompatible thoracic CT-scan images ;

2. Associated with one of the following criteria:

• positive detection of anti-Aspergillus IgG and/or precipitatinganti-aspergillus antibodies, according to the positivity threshold of thelaboratory performing the technique,

• positive direct examination of Aspergillus or positive culture, frombronchopulmonary samples (expectoration or endoscopic aspiration),

• revealing aspergillar hyphae/filaments on histological samples

3. Men or women age ≥ 18 years;

4. For the women of childbearing age: women having a negative serum pregnancy test,having a contraception highly effective and accepting to pursue it during at leastthe first 12 months of the study;

5. Patient legally free and not subject to any custody, guardianship, tutelage orsubordination measures;

6. Participants must be affiliated to France's Health Care Regime (" Sécurité Sociale ");

7. Free and informed consent signed by each participating patient.

Exclusion Criteria:

1.

• Patient affected with single aspergilloma

2.

• Patient presenting a contraindication to itraconazole (including allcontraindicated co-administrated medications as listed in the itraconazoleSmPc, including notably medications with potential to prolong theQT interval)

3.

• Patient presenting a contraindication to voriconazole and posaconazole (including all contraindicated coadministrated medications as listed in theSmPc)

4.

• Intolerance to beta2-agonists

5.

• Notion of relapse with isolation of an Aspergillus resistant to itraconazole

6.

• History of hypersensitivity reaction to liposomal amphotericin B or toitraconazole or to any other constituent

7.

• Patient having presented complications related to a previous treatment bynebulised LAmB

8.

• Patient received an oral (excepted oral Amphotericin B), parenteral orintra-cavity antifungal treatment within the last 2 months

9.

• Severe renal failure (clearance <30 ml / min).

10.

• Hepatic failure with transaminase and alkaline phosphatase values > 5 timesnormal

11.

• Significant abnormality of the blood cell and platelet counts (at thediscretion of the investigator)

12.

• Concomitant use of one or several of treatments contra-indicated with theexperimental or non-experimental treatment

13.

• Ventricular dysfunction such as congestive cardiac failure or history ofcongestive cardiac failure or patients with risk(s) factors of cardiacarrhythmia or symptomatic arrhythmia with a prolongation of the corrected QTinterval > 450 msec in men and 470 msec in women or treated by medication knownto prolong QT interval, or prolongation of the corrected QT interval > 450 msecin men and 470 msec in women.

14.

• Invasive pulmonary Aspergillosis, Allergic Bronchopulmonary Aspergillosis

15.

• Chronic Pulmonary Aspergillosis with indication for surgical interventionwithin 6 months from the start

16.

• Patients with Cystic Fibrosis

17.

• Immunocompromised patients

18.

• Threatening hemoptysis, with impossibility to defer surgical procedures (butpatients contraindicated to surgery may be included after resolution of thehemoptysis)

19.

• Tuberculosis or progressive non-tuberculous mycobacteria

20.

• Respiratory infection aggravating the underlying CPA (patient may be includedafter eradication of infection)

21.

• Patient refusing to participate

22.

• Protected majors in the meaning of the law, non affiliated persons or with nosocial security scheme, persons deprived of liberty by a judicial oradministrative decision, persons staying in a health or social institution,adults under legal protection, and finally patients in emergencies.

23.

• Patient in exclusion period following participation in another interventionalstudy evaluating antifungals or medicines

24.

• Women at age to procreate and not using highly effective contraception,pregnant or breastfeeding women