Inhaled GM-CSF Therapy of Autoimmune PAP
Autoimmune Pulmonary Alveolar Proteinosis
About this trial
This is an interventional treatment trial for Autoimmune Pulmonary Alveolar Proteinosis focused on measuring Whole lung lavage, GM-CSF, Sargramostim, aPAP
Eligibility Criteria
Inclusion Criteria:
- First step: only autoimmune PAP subjects will be included
Second step (eligibility for the WLL):
- presence of persistent or progressive respiratory failure (PaO2 at rest < 60 mm Hg)
- absence of respiratory failure at rest, but evidence for exertional
- desaturation < 90% or > 5 percentage points using the modified Bruce's protocol (5)
- careful evaluation of conditions contraindicating the WLL (see below)
- discussion with the patient about cost-effectiveness of the procedure and signature of the standard informed consent. Points a) and b) will be evaluated over a period of 3 months, to avoid spontaneous improvement or resolution.
(The former happens in 10% of cases falling in point b): in the case of fluctuation of saturation values around the threshold value, the procedure will be delayed until values are stable; the latter happened in 2/51 autoimmune PAP patients from our series, and the complete resolution occurred within the first 2 months from the diagnosis.)
- Third step (eligibility for the study): this step will be accomplished essentially by evaluation of the presence of conditions contraindicating the GM-CSF inhalation and upon ad hoc informed consent obtained from the patient
Exclusion Criteria:
- chronic lung disease associated with already existing respiratory failure (such as pulmonary emphysema or fibrosis)
- chronic heart failure or ischemic heart disease
- active pulmonary embolism
- progressive cancer
- other severe metabolic conditions
- secondary PAP
- previously experience of severe and unexplained side-effects during aerosol delivery of any kinds of agents
Sites / Locations
- Fondazione IRCCS Policlinico San Matteo
Arms of the Study
Arm 1
Arm 2
Experimental
Other
GM-CSF Group
Control Group
Scheduled Baseline WLL: All participants will receive scheduled bilateral WLL at baseline (month 0). GM-CSF induction treatment: All participants will receive inhaled GM-CSF (250 mcg daily, 7 consecutive days every other week for 12 weeks beginning 1 week after the scheduled baseline WLL). Washout period: All participants will not receive inhaled GM-CSF treatment for 4 weeks immediately following GM-CSF induction treatment. GM-CSF maintenance treatment: All participants will receive inhaled GM-CSF (250 mcg daily on days 1 and 3 of every consecutive 14-day period for 6 months beginning 17 weeks after the scheduled baseline WLL). Unscheduled Rescue WLL: Any participant experiencing progression of aPAP lung disease (defined as the disease progression resulting in respiratory failure (PaO2 at rest <60 mmHg of PaO2 > 60 mmHg at rest AND desaturation <90% at rest OR decline in SpO2 of 5% or more during exercise testing) will receive unscheduled rescue WLL.
Scheduled Baseline WLL: All participants will receive a scheduled bilateral WLL at baseline (month 0). Unscheduled Rescue WLL: Any participant experiencing progression of aPAP lung disease (defined as the disease progression resulting in respiratory failure (defined by a resting PaO2 <60 mmHg or > 60 mmHg and desaturation <90% at rest or decline in SpO2 of 5% or more during exercise testing) will receive unscheduled rescue WLL.