Please select the eligibility criteria that correspond to the clinical trial below.
Title: Antibiotic Treatment of Recurrent Episode of Asthma in Children - a Randomised, Case-controlled Study Within the COPSAC2010 Cohort (Asthma Begins in Childhood)
Brief Summary: Copsac has discovered that asthmatic exacerbations are as closely linked to bacterial as to viral infection. The current study will examine whether treatment of asthmatic exacerbations with macrolide antibiotics - in the abscence of clear clinical bacterial infection which would in any case precipitate antibiotic treatment - has an effect on either the particular episode, or subsequently. Macrolide antibiotics are chosen for ease of administration ensuring high compliance, antibiotic appropriacy, and anti-inflammatory properties.


Options:
A: Inclusion Criteria:

* 12-71 months of age.
* Recurrent significant wheezing in the past year (any of the following):

  * \>3 episodes, ≥1 of which was clinically significant\*; OR
  * \>2 clinically significant\* episodes; OR
  * \>4 months of daily controller therapy AND \>1 clinically significant\* episode.
  * \* Clinically significant episode: requiring any of the following: (1) systemic corticosteroids (oral or injectable), (2) unscheduled physician office visit, (3) ED visit, (4) urgent care visit, or (5) hospitalization.
* Up to date with immunizations, including varicella (unless the subject has already had clinical varicella). If the subject needs varicella vaccine, this will be arranged with the primary care physician and must be received prior to randomization.
* Willingness to provide informed consent by the child's parent or guardian.

Exclusion Criteria:

Participants who meet any of the following criteria are NOT eligible for enrollment, but may be re-enrolled if these exclusion criteria are resolved:

* \>4 courses of systemic corticosteroids in past 12 months.
* More than 1 hospitalization for wheezing illnesses within the preceding 12 months.
* Use of long-term controller medications for asthma, including inhaled corticosteroids, leukotriene modifiers, cromolyn/nedocromil, or theophylline for more than 8 months (cumulative use) in the past 12 months.
* Current use of higher than step 2 NAEPP asthma guideline therapy (e.g. medium-high dose ICS alone or combination therapy of low-medium-high dose ICS + LABA, montelukast, theophylline or cromolyn). NOTE: children who have evidence of well-controlled symptoms immediately preceding study entry while receiving Step 2 controller therapy (presence of self-reported symptoms on average no more than 2 times per week and less than 2 nights per month of nocturnal awakenings, requiring albuterol, during the 4 weeks preceding visit 1) may be enrolled and will have their controller therapy discontinued upon study entry.
* Use of OCS in the past 2 weeks.
* Daily symptoms or \>2 nocturnal awakenings, requiring albuterol, on average in the last 2 weeks.
* Use of antibiotics in the past month.
* Current treatment with antibiotics for diagnosed sinus disease.
* Participation presently or in the past month in another investigational drug trial.
* Evidence that the family may be unreliable or nonadherent, or may move from the clinical center area before trial completion.
* Contraindication of use of systemic corticosteroids or azithromycin.
* Clinically relevant gastroesophageal reflux.
* Concurrent medical conditions other than asthma that are likely to require oral or injectable corticosteroids during the study.
* If receiving allergy shots, change in dose within the past 3 months.

Participants who meet any of the following criteria are NOT eligible for enrollment, and may not be re-enrolled:

* Gestation less than late preterm as defined as birth before 34 weeks gestational age.
* Presence of lung disease other than asthma, such as cystic fibrosis and BPD. Evaluation during the screening process will assure that an adequate evaluation of other lung diseases has been performed.
* Presence of other significant medical illnesses (cardiac, liver, gastrointestinal, endocrine) that would place the study subject at increased risk of participating in the study.
* Immunodeficiency disorders.
* History of respiratory failure requiring mechanical ventilation.
* History of hypoxic seizure.
* History of significant adverse reaction to any study medication ingredient.
* The child has significant developmental delay/failure to thrive, defined as crossing of two major percentile lines during the last year for age and gender. If a child plots less than the 10th percentile for age and gender, a growth chart for the previous year will be obtained from the child's primary care provider.
B: 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
C: Inclusion Criteria:

* Participation in the COPSAC2010 cohort
* recurrent wheeze
* and others

Exclusion Criteria:

* Macrolide allergy
* Heart, liver or kidney disease.
* and others
D: 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

Answer: C