Please select the eligibility criteria that correspond to the clinical trial below.
Title: The AZIthromycin in Severe ASThma (AZISAST) Study: a Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Evaluating the Efficacy, Safety and Cost-effectiveness of Azithromycin as add-on Therapy in Adult Subjects With Severe Persistent Asthma, Who Remain Inadequately Controlled Despite GINA (2006) Step 4 or 5 Therapy
Brief Summary: The purpose of this study is to evaluate the efficacy, safety and cost-effectiveness of azithromycin as add-on therapy in adult subjects with severe persistent asthma, who remain inadequately controlled despite GINA (2006) step 4 or 5 therapy.


Options:
A: 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
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:

* Established diagnosis of COPD by medical doctor (based on clinical history OR pulmonary function test)
* Smoking history of at least 10 pack-years (10 pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years, etc.)
* Current hospitalization for potential infectious AECOPD treated with standard therapy
* History of at least one exacerbation during the last year (prior to the current hospital admission) for which systemic steroids and/or antibiotics were taken
* ECG at admission

Exclusion Criteria:

* Mechanical or non-invasive ventilation at moment of randomization (D1)
* Long QT interval on ECG (QTc \> 450msec for males or \> 470msec for females)
* History of life-threatening arrhythmias
* Myocardial infarction (NSTEMI or STEMI) less than 6 weeks before start of study drug
* Unstable angina pectoris or acute myocardial infarction (NSTEMI or STEMI) at admission
* Drugs with high risk for long QT interval and torsade de pointes (amiodarone, flecainide, procainamide, sotalol, droperidol, haldol, citalopram, other macrolides)
* Documented uncorrected severe hypokalemia (K+ \< 3.0 mmol/L) or hypomagnesemia (Mg2+ \< 0.5 mmol/L)
* Chronic systemic steroids (\> 4 mg methylprednisolone /day for ≥ 2 months)
* Actual use of macrolides for at least 2 weeks
* Allergy to macrolides
* Active cancer treatment
* Life expectancy \< 3 months
* Pregnant or breast-feeding subjects. Woman of childbearing potential must have a pregnancy test performed and a negative result must be documented before start of treatment
D: Inclusion Criteria:

Communities

* The community location in target district.
* The community leader consents to participation in the trial
* The community's estimated population is between 200-2,000 people.
* The community is not in an urban area.

Individuals - All children aged 1-60 months (up to but not including the 5th birthday), as assessed via biannual census.

Exclusion Criteria:

Individuals

- Refusal of village chief (for village inclusion), or refusal of parent or guardian (for individual inclusion)

Answer: B