Please select the eligibility criteria that correspond to the clinical trial below.
Title: Asthma Clinical Research Network (ACRN) Trial - Macrolides in Asthma (MIA)
Brief Summary: Asthma can be caused by a variety of factors, including tobacco smoke, allergens, and respiratory airway infections. Many people use inhaled corticosteroid medications to treat their symptoms. These medications, however, are not effective for everyone. Clarithromycin is an antibiotic that may effectively treat asthma in these individuals. This study will evaluate the effectiveness of clarithromycin at controlling asthma symptoms.


Options:
A: 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.
B: Inclusion criteria:

-Adults and adolescent participants with a physician diagnosis of asthma for ≥12 months, based on the Global Initiative for Asthma (GINA) 2014 Guidelines and the following criteria:

a) Existing treatment with medium to high dose ICS (≥250 mcg of fluticasone propionate twice daily or equipotent ICS daily dosage to a maximum of 2000 mcg/day of fluticasone propionate or equivalent) in combination with a second controller (eg, long-acting beta agonist, leukotriene receptor antagonist) for at least 3 months with a stable dose ≥1 month prior to Visit 1.

i) Note for Japan: for participants aged 18 years and older, ICS must be on ≥200 mcg of fluticasone propionate twice daily or equivalent; for participants aged 12 to 17 years, ICS must be ≥100 mcg of fluticasone propionate twice daily or equivalent).

ii) Participants requiring a third controller for their asthma will be considered eligible for this study, and it should also be used for at least 3 months with a stable dose ≥1 month prior to Visit 1.

Exclusion criteria:

* Participants \<12 years of age or the minimum legal age for adolescents in the country of the investigative site, whichever is higher (For those countries where local regulations permit enrollment of adults only, participant recruitment will be restricted to those who are ≥18 years of age).
* Weight is less than 30 kilograms.
* Chronic obstructive pulmonary disease or other lung diseases (eg, idiopathic pulmonary fibrosis, Churg-Strauss Syndrome, etc) which may impair lung function.
* A participant who experiences a severe asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids at any time from 1 month prior to the Screening Visit up to and including the Baseline Visit).
* Evidence of lung disease(s) other than asthma, either clinical evidence or imaging (Chest X-ray, CT, MRI) within 12 months of Visit 1 or at the screening visit, as per local standard of care.
* Note for Japan: According to the request from the health authority, chest X-ray should be performed at screening visit if there is no chest imaging (Chest X-ray, computed tomography \[CT\], magnetic resonance imaging \[MRI\]) available within 3 months prior to screening to exclude participants with suspected active or untreated latent tuberculosis.
* Current smoker or cessation of smoking within 6 months prior to Visit 1.
* Previous smoker with a smoking history \>10 pack-years.
* Comorbid disease that might interfere with the evaluation of Investigational Medicinal Product.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
C: Inclusion Criteria:

* healthy adults (≥ 18 years of age)
* non-pregnant
* free of any respiratory tract infection
* not having been administered any antibiotic at least in the past three months

Exclusion Criteria:

* \<18 years of age
* pregnant
* having a respiratory tract infection
* having been administered any antibiotic at least in the past three months
D: Inclusion Criteria:

* History of physician-diagnosed asthma
* Methacholine PC20 less than or equal to 16 mg/ml and/or FEV1 improvement greater than or equal to 12% in response to 180 mcg albuterol
* Stable asthma for at least 6 weeks prior to study entry
* FEV1 greater than or equal to 60% of predicted result following 180 mcg albuterol
* Juniper ACQ score greater than or equal to 1.5 (optimal ACQ score cut-off point for asthma that is "not well-controlled" by NIH/Global Initiative for Asthma \[GINA\] guidelines)
* Nonsmoker (less than 10 pack-per-year lifetime smoking history and no smoking in the year prior to study entry)
* Able to perform spirometry, as per American Thoracic Society criteria
* 75% adherence with diary cards, fluticasone (monitored with Doser), and placebo pill trial (monitored electronically with Electronic Drug Exposure Monitor \[eDEM\] pill dose counter) for the final 2 weeks of the four-week run-in period
* At Visit 1, in steroid-naïve participants, no significant adrenal suppression, defined as a plasma cortisol concentration less than 5 mcg/dL. If adrenal suppression occurs, a 250 mcg corticotropin (ACTH) stimulation test will be performed. Plasma cortisol levels will be collected at baseline, and 30 and 60 minutes after the ACTH stimulation test. Participants must have a cortisol concentration greater than 20 mcg/dL on at least one of the post-ACTH time points
* Absence of bronchoscopy-induced exacerbation; if bronchoscopy-induced exacerbation has occurred, prednisone therapy must have stopped at least 6 weeks prior to study entry
* Absence of respiratory tract infection; if infection has occurred, infection-related symptoms must have stopped at least 6 weeks prior to study entry
* Has experienced no more than two exacerbations or respiratory tract infections prior to study entry
* If female and able to conceive, willing to utilize two medically acceptable forms of contraception (one non-barrier method with single barrier method OR double barrier method)

Exclusion Criteria:

* Presence of lung disease other than asthma
* Presence of vocal cord dysfunction, due to potential confounding of ACQ score
* Significant medical illness other than asthma
* History of atrial or ventricular tachyarrhythmia
* Use of any medication that has a significant interaction with clarithromycin, including herbal or alternative therapies
* Asthma exacerbation within 6 weeks of the screening visit or during the run-in period prior to bronchoscopy
* Use of systemic steroids or change in dose of controller therapy within 6 weeks of the screening visit
* Inability, in the opinion of the study investigator, to coordinate use of dry powder or metered-dose inhaler or to comply with medication regimens
* Inability or unwillingness to perform required study procedures
* Prolonged heart rate corrected QT-interval (greater than 450 msec in women and greater than 430 msec in men) on echocardiogram (ECG) at study entry
* Low potassium or magnesium levels (based on local Asthma Clinical Research Network laboratory definitions)
* Abnormal elevation of liver function tests (AST, ALT, total bilirubin, or alkaline phosphatase)
* Abnormal prothrombin time (PT) or partial thromboplastin time (PTT) results
* Reduced creatinine clearance
* Contraindication to bronchoscopy, as determined by medical history or physical examination
* Regular consumption of grapefruit or grapefruit juice
* Pregnant or breastfeeding

Answer: D