• Standard lung function parameters (FEV1, FVC, FEV1/FVC, MEF) [ Time Frame: baseline vs week 4 ]
• AAT activity in induced sputum [ Time Frame: baseline vs week 4 ]
• total IgG fragments in induced sputum [ Time Frame: baseline vs week 4 ]
• total bacterial load in induced sputum [ Time Frame: baseline vs week 4 ]
• Pseudomonas load in induced sputum [ Time Frame: baseline vs week 4 ]
• Neutrophil number in induced sputum [ Time Frame: baseline vs week 4 ]

The objective of this trial is to determine the optimal region of the lung for depositing Prolastin (alpha-1 antitrypsin; AAT) by inhalation in order to treat cystic fibrosis (CF). The AKITA® nebulizer has settings which can be varied to target the inhaled drug to either the deep lung or to the upper airways in a one to one randomization. The study will measure how much of the activity of the enzyme elastase is inhibited by AAT.

The optimum deposition site (bronchial or peripheral) in CF patients for AAT will be investigated by measuring several parameters in induced sputum. The study will start with a 2 week run-in period in which the planned 60 patients inhale isotonic saline once daily. This period is followed by a 4 week treatment period where 30 patients inhale AAT for peripheral deposition and 30 patients inhale AAT for bronchial deposition. Six patients in each group will be asked to collect spontaneous sputum at home.

Twenty-five milligrams of AAT will be deposited at one of the two target sites using the AKITA® device. The inhalation should take place in the evening between 18.00 and 23.00 h.

Patients will inhale saline once daily for 2 weeks (run-in period) followed by 4 weeks of once daily inhalation of AAT. Induced sputum will be collected at visits to the clinic at the start of the run-in, at the start of AAT treatment, and at 2 and 4 weeks after the start of AAT treatment.

• Experimental: Bronchial Deposition
• Experimental: Peripheral Deposition

Inclusion Criteria:

• Patient with diagnosis of CF
• Age >= 8 years
• FEV1 > 25 % of predicted value
• Free elastase activity checked at visit 1 must be positive (free elastolytic activity in the sample, 2 standard deviations above of the negative blank samples in the assay.) .
• Patient must be positive at least 3 times for pseudomonas in the last 2 years
• Patient must be positive for pseudomonas at Visit 1
• Patient must be able to perform reliable spirometry
• Patient must be on stable concomitant therapy at least 2 weeks prior to visit 1 and during the study
• Written informed consent of the patient or legal representative(s)

Exclusion Criteria:

• FEV1 < 25% of predicted value post-bronchodilator
• History of lung transplant
• Any lung surgery within the past 2 years
• On any thoracic surgery waiting list
• Severe concomitant disease (serious malignant disease, congestive heart failure NYHA III/IV, cor pulmonale with the need of oxygen therapy)
• Severe liver cirrhosis with ascites, hypersplenism or grade III/IV esophageal varices.
• Known selective IgA deficiency with known antibody against IgA (anti-IgA antibody)
• Active pulmonary exacerbation within the 4 weeks prior to screening
• Current Smoking
• Pregnancy or lactation
• Women of child-bearing age without adequate contraception
• Any medical condition which the investigator feels will prohibit the patient from completing the trial
• Participation in another clinical trial within 30 days prior to inclusion at visit 1