Please select the eligibility criteria that correspond to the clinical trial below.
Title: Bronchiectasis and Long Term Azithromycin Treatment: A Randomised Placebo-controlled Trial Studying Disease Modifying Effects of Immunomodulating Treatment
Brief Summary: 1. SUMMARY

Rationale: Patients with bronchiectasis often experience lower respiratory tract infections with progression of symptoms and decline in quality of life. Macrolides, as has been shown in panbronchiolitis and cystic fibrosis, may break or weaken the link between infection and inflammation resulting in an improvement of symptoms. Also the number of exacerbations may lowered.

Objective: A reduction in number of infective exacerbations and improvement in lung function by AZT treatment are the primary objectives. Secondary objectives that will be evaluated are: symptoms score, quality of life, inflammatory parameters, bacterial colonisation, and adverse events.

Study design: Randomised double blind multicenter study in the Netherlands. Patients will be stratified for colonisation with P.aeruginosa.

Study population: Patients with bronchiectasis demonstrated by high-resolution computed tomography (HR-CT) scan or bronchography.

Intervention: Patients receive Azithromycin 250mg(p.o.) once daily or placebo.

Main study parameters/endpoints: Reduction in number exacerbations, defined as increase symptoms such as dyspnoea, coughing, and sputum production for which a course of prednisolone and/or antibiotic is needed. Change in lung function parameters (forced expiratory volume in 1 second \[FEV1\], forced vital capacity \[FVC\]) measured by spirometry is the other primary endpoint.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risk of participating in this study is low. Laboratory, radiographic examinations, and pulmonary function tests are commonly used as diagnostic procedures during outpatients visits and during exacerbations. Adverse effects in maintenance treatment with AZT are usually mild and mainly gastrointestinal. Sometimes rash and abnormal liver function tests are observed. A better quality of life will probably be the beneficial effect of long term treatment with AZT. This will be achieved by a reduction in respiratory and non-respiratory symptoms and number of exacerbations.


Options:
A: Inclusion Criteria:

* Patients aged 18 ≥ years
* Bronchiectasis diagnosed by plain bronchography or high resolution computer tomography.
* Minimal 3 lower respiratory tract infections (LRTI) treated with oral/intravenous (IV) antibiotics in the year preceding the study inclusion.
* The presence of chronic respiratory symptoms such as cough, dyspnoea, expectoration of sputum.
* At least one positive sputum culture in the preceding year.
* Informed consent

Exclusion Criteria:

* Previous ( ≥ 4 weeks) prolonged macrolide therapy.
* Pregnant or lactating women.
* Allergy to macrolides.
* Intolerance to macrolides.
* Liver disease (alanine transaminase and/or aspartate transaminase levels 2 or more times the upper limit of normal).
* Use of antibiotics within 14 days of screening.
* Use of oral or IV corticosteroids (≥ 30 mg prednisolone/daily) within 30 days of screening.
* Other research medication started 2 months prior to inclusion.
B: Inclusion Criteria:

1. patients who have given written informed consent
2. males or females of any race
3. 18-75 years of age
4. with the diagnosis of persistent asthma ≥ 1 year duration at screening and a history consistent with GINA step 4 or 5 clinical features
5. receiving high dose ICS plus inhaled LABA for at least 6 months prior to screening
6. patients who have suffered multiple (i.e. at least two) independent documented severe asthma exacerbations within the previous 12 months
7. patients must be never-smokers or ex-smokers with a smoking history of ≤ 10 pack-years.

Exclusion Criteria:

1. females who are pregnant or who are breastfeeding
2. patients with severe bronchiectasis
3. patients with active tuberculosis or non-tuberculous mycobacterial infections (NTM)
4. patients with significant underlying medical conditions (e.g. infection, hematological disease, malignancy, neurologic, renal, hepatic, coronary heart disease or other cardiovascular disease, endocrinologic or gastrointestinal disease) within the previous 3 months
5. who are unable to perform spirometry or complete a patient diary or complete questionnaires
6. patients with known hypersensitivity to azithromycin or other macrolide antibiotics
7. patients who's heart rate corrected QT interval is prolonged
8. patients who have - in the judgement of the investigator - a clinically relevant laboratory abnormality
9. patients currently treated with macrolide antibiotics or recent macrolide treatment (in the past twelve weeks)
10. anti-IgE treatment
C: Inclusion Criteria:

* Age 1-59 months,
* Plan to remain in study area greater than 6 months
* Discharged from hospital following non-trauma related admission

Exclusion Criteria:

* Contraindication to azithromycin use and other prophylactic antibiotic use
D: Inclusion Criteria:

1. Diagnosis of chronic lung disease (defined as FEV1 and/or FVC \<80% predicted)
2. Age 6-19 years
3. Perinatally-acquired HIV infection the most likely source of transmission
4. On first or second-line ART for at least one year
5. HIV-1 viral load undetectable (as defined by each trial site)
6. A firm home address accessible for visiting and intending to remain there for 24 months
7. Willing to agree to participate in the study and to give samples of blood and sputum
8. HIV status disclosed to child for those aged older than 12 years

Exclusion Criteria:

1. Any condition (except HIV) that may prove fatal during the study period (e.g. malignancy, end-stage HIV disease or other conditions deemed likely fatal by the trial physician)
2. Diagnosis of active pulmonary TB
3. Infection with non-tuberculous mycobacteria (NTM)
4. Pregnant or breast-feeding
5. Condition likely to lead to lack of understanding of study procedures or to uncooperative behaviour e.g. neurocognitive disease, developmental delay or psychiatric illness
6. History of prolonged QTc syndrome or current or planned therapy with drugs likely to cause cardiac dysrhythmias
7. Abnormal ECG findings
8. Acute respiratory tract infection during enrolment (patients will be eligible once their acute infection is treated)
9. Creatinine clearance of \<30mls/minute
10. ALT more than 2 times the upper limit of normal
11. No defined guardian/stable caregiver
12. No consent/assent from guardian/child

Answer: A