Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of Macrolides on Asthma Control, Airway Inflammation and Bacterial Colonisation in Smokers With Asthma.
Brief Summary: Asthma is a common disease in Westernised societies, affecting up to 10% of the population. Corticosteroids are the most effective treatment for asthma but the therapeutic response varies considerably between individuals. A major cause of corticosteroid insensitivity in asthma is cigarette smoking. Active cigarette smoking occurs in over 25% of adults with asthma and a further 25% are ex-smokers. In a series of proof of concept clinical studies the investigators demonstrated for the first time that the efficacy of inhaled and oral corticosteroids is markedly impaired in smokers with asthma and to a lesser extent in ex-smokers with asthma. Active cigarette smoking has other detrimental effects on asthma morbidity including more severe symptoms, increased rates of hospitalisation, and accelerated decline in lung function. Smoking cessation advice is often ineffective because many adult smokers with asthma do not believe that they are personally at risk from their smoking, take many years until stopping smoking and frequently restart smoking after quitting. Alternative or additional drugs to corticosteroids are needed for smokers with asthma who are unable to obtain the clinical benefits associated with stopping smoking. In a proof of concept clinical trial the investigators will test the hypothesis that macrolides improve asthma control and reduce sputum neutrophil counts of smokers with chronic asthma.


Options:
A: Inclusion Criteria:

* Diagnosis of asthma
* Age 18-70
* Current smoker
* Duration of symptoms \>1yr with stability for 4 weeks
* Able to maintain asthma without exacerbations during run in period
* Able to wean off other asthma medication

Exclusion Criteria:

* Ex-smokers or never smokers
* Planning to quit smoking during duration of trial
* Patients with unstable asthma
* Patients with current epilepsy, psychosis or history of significant atrial or ventricular tachyarrhythmia
* Corrected QT-interval greater than 450msec in women, 430msec in men
* Low potassium levels. If can be corrected then screening can continue with confirmation of normal levels prior to taking study medication
* Liver disease (ALT and/or AST levels 2 or more times ULN)
* Significant renal disease (Creatinine or urea levels 2 or more times ULN)
* Any previous severe adverse reactions to macrolides
* Patients who are known to have specific IgE sensitivity or skin test positivity to grass pollen and a history of worsening of asthma due to hay fever will not be recruited from mid May to the end of July
* Upper or lower respiratory tract infection in the 4 weeks prior to randomisation. Run in period can be prolonged in this situation to have 4 weeks with no respiratory infection prior to randomisation.
* Patients who require medications known to interact with azithromycin
* On other immunosuppressants or chronic antibiotics
* Weight less than 45kg
* Frequent asthma exacerbations (greater than 4) requiring oral corticosteroids in the year prior to randomisation
* Current or past diagnosis of allergic-bronchopulmonary-aspergillosis
* Pregnancy and breast feeding
* Mental impairment or language difficulties that makes informed consent not possible
B: Inclusion Criteria:

* Have provided written informed consent to participate in the study in accordance with the local ethics committee regulations
* Have a confirmed diagnosis of bronchiectasis (by HRCT) Aged 18 years or over Have chronic sputum production, defined as a greater than 45 mililitres volume produced in the 1 week prior to study entry.
* Be able to perform reproducible spirometry
* Be in a relatively stable disease state in the 6 weeks prior to entry, as defined by the absence of the following: respiratory exacerbations requiring hospitalisation, change in cough and/or sputum production, new or increased hemoptysis, more than 10% weight loss, use of additional antibiotic courses

Exclusion Criteria:

* Subjects will be excluded if one or more of the following criteria occur. The subject: Is an investigator, or an immediate family member of an investigator
* Has a confirmed diagnosis of cystic fibrosis, as evidenced by genetic analysis or a sweat test result more than 60mmol/L
* Has a primary immunodeficiency Is a pregnant or lactating female Has had a respiratory exacerbation requiring hospitalisation or additional course of antibiotics in the 6 weeks prior to study entry
* Has been prescribed or used oral steroids on any occasion for the 3 months prior to study entry.
* Has been using mucolytic agents on any occasion for the 2 months prior to study entry Has active tuberculosis
* Has an active malignancy, including melanoma (other skin carcinomas excluded)
* Has a history of significant liver disease or insufficiency Has a significant history of drug abuse (including alcohol abuse) or mental illness Has a known intolerance or allergy to macrolides
* Has been participating in another interventional drug study in the 3 months prior to enrolment into this study
C: 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)
D: 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

Answer: A