The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis

• Quality of Life Assessment with St George's Respiratory Questionnaire(SGRQ) and Leicester Cough Questionnaire(LCQ) [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  

• Mean number of exacerbations per patient per 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  Exacerbations defined by persistent (≥ 24 h) deterioration in at least three respiratory symptoms, including cough, dyspnea, hemoptysis, increased sputum purulence or volume, chest pain (with or without fever).
  
  
• Changes of sputum characteristics from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• Changes of 24 hour sputum volume from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• Changes of forced expiratory volume in 1 second(FEV1) from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• Changes of mean forced expiratory flow between 25% and 75% of the FVC(FEF25-75)from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• Changes of forced vital capacity(FVC) from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• Changes of peak expiratory flow(PEF) from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• Induced sputum cytology count [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• Changes of sputum culture from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• IL-6 [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  Test IL-6 both in blood and sputum.
  
  
• IL-8 [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  Test IL-8 both in blood and sputum.
  
  
• IL-10 [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
  Test IL-10 both in blood and sputum.
  
  
• Tumor necrosis factor(TNF)α [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  Test TNF-α both in blood and sputum.
  
  
• Activity of histone deacetylase(HDAC) [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  HDACs are extracted from cells in blood.
  
  
• Activity of histone acetyltransferase(HAT) [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  HATs are extracted from cells in blood.
  
  
• 8-Isoprostane [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• Neutrophilic granulocytes in blood routine examination [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• White blood cells in blood routine examination [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• Monocytes in blood routine examination [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• Eosinophilic granulocytes in blood routine examination [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  
• Number of participants with Adverse events as a measure of safety and tolerability [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  Adverse events may contain symptoms such as nausea, sickness, headache, insomnia, palpitation, arrhythmia and so on. Record the symptoms and times of the patients.
  
  
• Plasma Concentration of Theophylline [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  Venous blood was taken for plasma theophylline at the end of the treatment period. (At the very time of 2 hours after patients taken the pills)
  
  

Non-cystic fibrosis bronchiectasis is an orphan disease caused by the pathogenic vicious circle including infection, inflammation and airway repair. Today's principle of treatment is to break the cycle of inflammation and infection. Nowadays, most clinical trials are anti-infective treatment by antibiotics trying to break this cycle by reducing the bacterial load, which may cause bacterial resistance. There were still some anti-inflammation trials by using inhaled corticosteroids(ICS). Tsang and Martínez-García showed that inhaled corticosteroids reduced IL-1,IL-8 levels and sputum inflammation cells, and improved sputum volume as well as quality of life, though the corticosteroid must be high dose or medium dose combined with long-acting ß2 adrenergic agonists. As described in asthma and chronic obstructive pulmonary disease(COPD), theophylline can improve the activity of histone deacetylase (HDAC) and then enhanced the anti-inflammatory effect of steroids. We hypothesis that theophylline may have the same effect in subjects with bronchiectasis. Theophylline plus inhaled low-dose formoterol-budesonide may improve quality of life and reduce airway inflammation.