Inhaled A1AT in Adult Stable Bronchiectasis
Condition: Bronchiectasis Adult
MeSH terms: Bronchiectasis
Study type: Interventional

Summary: 
      Aim: to investigate the influence of alpha1-antitrypsin (A1-AT) nebulization on levels of
      A1-AT in BAL and plasma in patients with stable bronchiectasis.

      Method: single-blind placebo-controlled randomised clinical trial. 19 stable bronchiectasis
      patients with chronic bronchial infection and 10 control patients (without bronchiectasis)
      underwent a bronchoscopy in order to assess levels and inhibitory capacity of A1AT and
      neutrophilic elastase. Afterwards, the 19 bronchiectasis patients were randomly allocated to
      receive inhaled A1AT 250mg diluted in 10ml 0.9% saline solution once a day for a month (Group
      A, n: 10) or placebo (10ml 0.9% saline solution; group B, n: 9). A new BAL was performed in
      both groups (A and B) 24 hours after the end of treatment (1month) to re-analyze A1AT and NE.
    

Detailed description: 
      Effects of inhaled alpha-1-anti-trypsin in bronchiectasis patients with chronic bronchial
      infection.

      Introduction: one of the main features of bronchiectasis is chronic and deregulated
      neutrophilic bronchial inflammation. Excessive neutrophilic elastase (NE) activity has been
      widely described as part of the characteristic imbalance between proteases and
      anti-proteolytic enzymes that characterizes airways inflammation and progressive lung damage
      in bronchiectasis.

      Alpha-1-antitrypsin (A1AT) is a protease inhibitor involved in protecting lung tissue from
      enzymes of inflammatory cells, including neutrophilic elastase, and its concentration rises
      in case of acute and chronic inflammation. Its reduction or absence is associated with the
      development of a specific kind of emphysema in case of exposure to tobacco smoking.

      Moreover it is likely that its levels could be reduced in bronchiectasis as a consequence of
      chronic bronchial infection and inflammatory deregulation.

      Aims:

        1. concentrations of total and free NE, NE inhibitory capacity and A1AT levels were
           investigated in broncho-alveolar lavage (BAL) of bronchiectasis patients with chronic
           airways infection in stable conditions in comparison with a control group (patients
           without bronchiectasis)

        2. The effects of inhaled A1AT (Prolastin) on BAL concentration of total and free NE and
           A1AT and inhibitory capacity of NE were assessed after one month of treatment in
           patients with bronchiectasis and chronic bronchial infection (placebo controlled trial)
           Study design: simple blind placebo-controlled randomized clinical trial

      Methods:

      19 patients with stable non cystic fibrosis bronchiectasis and chronic bronchial infection
      and 10 patients without bronchiectasis (control group) underwent a bronchoscopy to perform
      BAL analysis.

      The 19 bronchiectasis patients were randomly allocated to receive inhaled A1AT 250mg diluted
      in 10ml 0.9% saline solution once a day for a month (Group A, n: 10) or placebo (10ml 0.9%
      saline solution; group B, n: 9). A new BAL was performed in both groups (A and B) 24 hours
      after the end of treatment (1month) to re-analyze A1AT and NE.

      Clinical, microbiological, biochemical, functional and radiological characteristics of
      bronchiectasis and potential side effects of treatment on both arms were also recorded before
      (baseline), at 7, 15, 30 days of treatment and at 1 and 2 months follow-up visits after the
      end of treatment. The trial was approved by Spanish Ministry of Health (Trial nº 95/256) and
      local Ethics Committee (AC(HG) 44/95) and all patients signed written consent.
    

Intervention name(s): Group A; Group B
Intervention type(s): Drug; Drug
Intervention description(s): one nebulization with 250mg alpha-1-antitrypsine diluted in 10ml injectable solution once a day during 1 month. A CR-60 high flow compressor and Ventstream nebulizer were used for nebulization.; 10ml of 0.9% NaCl saline solution nebulised once daily for 1 month. A CR-60 high flow compressor and Ventstream nebulizer were used for nebulization.
Other intervention name(s): inhaled Prolastin (nebulized alpha1-antitrypsin); placebo
Intervention MeSH terms: Alpha 1-Antitrypsin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 2 parallel groups of patients with bronchictasis were investigated: 1 receiving inhaled prolastina and 1 receiving placebo (saline solution) all bronchiectasis patients were initially compared with 10 control patients with no bronchiectasis
Masking: Single (Investigator)
Primary purpose: Supportive Care
Keywords: bronchiectasis; alpha1-antitrypsin; neutrophilic elastase