Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Oral Azithromycin (500 Mg OD) as a Supplement to Standard Care for Adult Patients With Acute Exacerbations of Asthma
Brief Summary: Acute attacks (exacerbations) of asthma are common and cause a great deal of suffering in asthmatic patients. Current treatments for asthma attacks are not completely effective and new and better treatments are needed. Viruses often cause asthma attacks and bacterial lung infections have also been associated with asthma attacks. However, the role for bacteria is uncertain. Current asthma guidelines for doctors treating asthma exacerbations do not recommend the routine use of antibiotics. The investigators would like to investigate whether or not azithromycin, which is a safe and well tolerated antibiotic (an antibacterial) that has been used for many years in the treatment of respiratory disease, might be of benefit in asthma attacks. As there is some evidence that azithromycin has anti-viral properties this may add to its benefits (antibiotics don't usually affect viruses). By looking at the effect of azithromycin on asthma attacks this will help us to show whether or not azithromycin should be recommended during an acute asthma attack in addition to the usual care that is provided to these patients as it may help them recover quicker from the exacerbation. The investigators will also be able to look at why azithromycin may be effective - if it is having an anti-bacterial and/or anti-viral effect.


Options:
A: Inclusion Criteria:

* Stable LTx recipients at discharge after transplantation.
* Signed informed consent
* Adult (age at least 18 years old at moment of transplantation)
* Able to take oral medication

Exclusion Criteria:

* Prolonged and/or complicated ICU-course after transplantation.
* Early (\<30 days post-transplant) post-operative death
* Major suture problems (airway stenosis or stent)
* Retransplantation (lung)
* Previous transplantation (solid organ)
* Multi-organ transplantation (lung+ other solid organ)
B: Inclusion Criteria:

* Clinical diagnosis of at least moderate Chronic Obstructive Pulmonary Disease (COPD), as defined by the following Global Initiative for COPD (GOLD) criteria:

  1. Post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio of less than 70%
  2. Post-bronchodilator FEV1 less than 80% predicted, with or without chronic symptoms
* Cigarette consumption of 10 pack-years or more (may or may not be active smokers)
* Meets one or more of the following four conditions:

  1. Current, or history of, supplemental O2 use
  2. Received a course of systemic corticosteroids for respiratory problems within 1 year prior to study entry
  3. Visited an emergency department for a COPD exacerbation within 1 year prior to study entry
  4. Hospitalized for a COPD exacerbation within 1 year prior to study entry
* Willing to make return visits
* Available by telephone for duration of study
* Minimum of 4 weeks from the most recent acute exacerbation (have not received a course of systemic corticosteroids, an increased dose of chronically administered systemic corticosteroids, and/or antibiotics for an acute exacerbation for a minimum of 4 weeks from the time of study entry)

Exclusion Criteria:

* Diagnosis of asthma
* Diagnosis other than COPD that results in the patient being either medically unstable, or having a predicted life expectancy less than 3 years
* Special patient groups (i.e., prisoners, pregnant women, or institutionalized patients)
* Women who are at risk of becoming pregnant during the study (pre-menopausal) and who refuse to use acceptable birth control (i.e., hormone-based oral or barrier contraceptive) for the duration of the study
* History of hypersensitivity to any macrolide antibiotic
* Taking any of the following medications:

  1. Cisapride
  2. Ergot derivatives
  3. Pimozide
  4. Disopyramide
  5. Cyclosporin
  6. Tacrolimus
  7. Nelfinavir
  8. Bromocriptine
  9. Hexobarbital
* Corrected QT interval (QTc) on electrocardiogram exceeding 440 ms
* Taking rifabutin or rifampin
* Chronic hepatic insufficiency
* Chronic renal insufficiency
* Diagnosis of bronchiectasis (defined as production of greater than one-half cup of purulent sputum/day)
* If, for either ear, formal audiometric testing in a sound booth results in a pure tone average (i.e., the average of the thresholds for the 4 frequencies 1000, 2000, 3000, or 4000) exceeding 50 decibel (dB), or if the threshold at any one frequency exceeds 60 dB, then the participant will be counseled by the audiologist concerning hearing aids and/or referral to an otolaryngologist. In addition, the audiologist may discuss with the participant whether or not to continue in the study. Following the examination and counseling, the participant will also discuss whether or not to continue in the study with one of the study investigators. If it is found that a participant's pure tone average in the two ears differs by more than 15 dB, or if the difference in the two ears for any one frequency exceeds 20 dB, then the participant will not be eligible for randomization into the study unless cleared by an otolaryngologist
C: 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
D: Inclusion criteria

Patients meeting all of the following criteria will be considered for admission to the study:

* Adults, either sex, ages 18-55 years or age 56 to 65 with \< 20 pack year smoking history or \>65 with \<5 pack year smoking history
* Patients with a documented history of asthma for \>6 consecutive months, and
* Patients presenting within 48 hours (of initial presentation to medical care) with an acute deterioration in asthma control (increased wheeze, dyspnea and/or cough and/or reduced PEF) and requiring a course of oral steroids
* Patients with a PEF or FEV1 less than 80% of predicted normal or patient's best at presentation, at recruitment or in the time elapsed between presentation and recruitment
* Patients must be able to complete diaries and quality of life questionnaires.
* Patients must sign and date an informed consent prior to any study procedures.

Exclusion criteria

Patients presenting with any of the following will not be included in the study:

* Patients with known prolongation of the QT interval, a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure, patients on drugs known to prolong the QT interval and patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, aminodarone, sotalol) antiarrhythmic agents.
* Smokers aged 56-65 with a \>20 pack year history, or aged \>65 with \>5 pack year history
* Patients requiring immediate placement in ICU
* Patients who used oral or systemic antibiotics within 28 days prior to enrolment
* Patients with known impaired hepatic function (ALT/AST \> 2 ULN)
* Patients with significant lung disease (including COPD) other than asthma
* Patients with \> 20mg oral corticosteroid maintenance therapy
* Patients requiring other antibiotic therapy
* Patients who are receiving other medications or who have other disease conditions or infections that could interfere with the evaluation of drug efficacy or safety
* Women who are breast-feeding or are pregnant, as demonstrated by a urine pregnancy test carried out before exposure to study medication or the start of any study procedure that could pose a risk to the foetus
* Patients with suspected or known hypersensitivity to, or suspected serious adverse reaction to Azithromycin or any of the macrolide or ketolide class of antibiotics, erythromycin or to any excipients thereof
* Patients who have received treatment with any other investigational drug within 1 month prior to study entry, or have such treatment planned for the study period during treatment and follow up phase
* Patients with a concomitant condition (including clinically relevant cardiovascular, hepatic, neurologic, endocrine, or other major systemic disease) making implementation of the protocol or interpretation of the study results difficult
* Patients with mental conditions rendering them unable to understand the nature, scope, and possible consequences of the study.
* Patients unlikely to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits.
* No subject will be allowed to enrol in this study more than once.

Answer: D