Please select the eligibility criteria that correspond to the clinical trial below.
Title: Evaluation of the Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation
Brief Summary: The occurrence of bronchiolitis obliterans syndrome (SBO) after allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be a chronic pulmonary graft versus host disease (GVHD) that is associated with significant mortality and morbidity. The reported incidence of SBO varies from 6 to 26% of allogeneic HSC recipients and is usually diagnosed within 2 years after transplantation. The diagnosis of SBO relies on the occurrence of a new airflow obstruction identified during pulmonary function testing, and the definition differs between studies. Currently, no curative immunosuppressive treatment is available, and recent data suggest that the use of these treatments, especially corticosteroids, should be limited because of their toxicity. The impairment of lung function parameters is likely caused by fibrous small airway lesions. Few data on the pathogenesis of SBO after allogeneic HSCT are available. Several hypotheses are based on the occurrence of SBO during chronic graft rejection after lung transplantation, which shares many clinical and histopathological similarities with SBO after allogeneic HSCT. One hypothesis is that the first step leading to SBO is lung epithelium injury. SBO is then identified as an alloimmune reaction with only one clearly identified risk factor: extrathoracic chronic GVHD. Due to their anti-inflammatory and immunomodulatory properties, recent data suggest that low-dose macrolides may be effective at preventing SBO after lung transplants. This well-tolerated treatment may be useful for preventing SBO after allogeneic HSCT.

The objective of this Phase 3 multicentre randomized, double-blinded, clinical trial is to evaluate the efficacy of azithromycin in preventing BO syndrome after allogeneic HSCT in patients with malignant hematological diseases.


Options:
A: Inclusion Criteria:

* Patients \> 40 years of age, in our outpatient clinic with chronic cough and COPD (gold2-4)
* Chronic cough is defined as a cough \> 12 weeks duration, at least 12 weeks a year in 2 subsequent years.
* Analysed for bronchiectasis prior to participation by CT-thorax.

Exclusion Criteria:

* Prior history of asthma
* Use of i.v. or oral corticosteroids and or antibiotics for an exacerbation 3 weeks before inclusion
* Patients suffering from other relevant lung diseases.
* Clinically relevant abnormal laboratory values suggesting an unknown disease requiring further clinical evaluation.
* Liver disease, (ALAT and/or ASAT levels two or more times the upper limit of normal).
* Pregnancy or lactation.
* Use of macrolides the last 6 weeks prior to inclusion.
* Allergy or intolerance to macrolides.
* Other research medication started 2 months prior to inclusion.
* Prior randomisation in this study.
B: Inclusion Criteria:RA according to the 1987 American Rheumatism Association criteria19, age between 18 and 70 years. Patients were required to have had an inadequate response to one to four DMARDs (such as azathioprine, methotrexate, sulfasalazine, penicillamine, hydroxychloroquine, or oral or injectable gold); an inadequate response was defined as discontinuation of therapy because of lack of effect. If patients were receiving DMARDs, they were required to complete a DMARD washout period that lasted at least 1 month before starting study drug treatment; no DMARDs were permitted during the study. Patients who were receiving nonsteroidal antiinflammatory drugs, prednisone (at 10 mg daily or less), or both were eligible if the doses had been stable for at least four weeks before the study period and continued to be stable during the study period. Patients were not allowed to receive intra-articular corticosteroids.

Patients had to have active disease at enrollment (before the DMARD washout period), defined as 12 or more tender joints, 10 or more swollen joints, and at least one of the following: erythrocyte sedimentation rate(ESR) of at least 28 mm/hr, C-reactive protein(CRP) level greater than 2.0 mg/dL, or morning stiffness for at least 45 minutes.

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Exclusion Criteria:

* A negative pregnancy test result was required for non-menopausal female patients. In female patients of childbearing potential a urine pregnancy test was done at baseline and any pregnant women were excluded. Other exclusion criteria included impaired hepatic enzyme tests, impaired renal function, chronic/recurrent infection (e.g., chronic bronchitis, recurrent sinusitis), other infections(e.g., Borrelia burgdorferi, Chlamydia trachomatis, Ureaplasma) , history of adverse reactions to macrolides, roxithromycin, or similar antibiotics.

A patient could be withdrawn from the trial at any time after enrollment for the following reasons: the patient's request, severe or life-threatening adverse event, or inadequate control of arthritis symptoms (\>50 percent increase in the total number of swollen or tender joints) necessitating an increase in the systemic corticosteroid dosage or reinstitution of therapy with disease-modifying antirheumatic drugs.
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\> 16 years old
* Experimenting an allogeneic HSCT for a hematologic malignancy
* Pre-transplantation Pulmonary Function Testing
* With written informed consent

Exclusion Criteria:

* Allergy or Intolerance to azithromycin, macrolides or ketolide or excipient
* Prolonged corrected QT (QTc) interval (\>450 msec)
* Taking medications that prolong the QTc interval (Cisapride, ergotamine, dyhydroergotamine)
* Taking ergotamine and dyhydroergotamine due to the risk of ergotism
* Family history of a prolonged QTc interval.
* History of congestive heart failure
* Taking colchicine Severe liver insufficiency • History of infection due to atypical mycobacteria

Answer: D