Patient case (clinical description): A 30-year-old man who is a computer scientist came to the clinic with the lab result stating azoospermia.  The patient is sexually active with his wife and does not use any contraception methods.  They have been trying to conceive for the past year with no success.  The patient has a past medical history of recurrent pneumonia, shortness of breath, and  persistent cough that produces large amounts of thick sputum. The patient had multiple lung infections during childhood. He does not smoke, use illicit drugs or alcohol.  The patient has no history of other medical conditions including allergies or any kind of surgery.  On physical examination, the digits show clubbing.  An ultrasound shows bilateral absence of the vas deferens, and FEV1 was 75% on the respiratory function test.

Patient's own account: I'm a 30-year-old computer scientist. I did some lab tests that came back quite alarming, stating that I have azoospermia?! I'm sexually active with my wife and we don't use contraception. We've been trying to have a child for the past year. I have a medical history of pneumonia and shortness of breath and regular wet cough. I had several lung infections when I was a kid. That's why I'm very careful and don't smoke, do drugs, or drink. I don't have other medical conditions including allergies or any kind of surgery. The doctor did the clubbing test on my fingers, which was positive. I also did an ultrasound and it showed that I'm missing the tubes that carry sperm around. I also had a 75% for my respiratory function test.

Clinical trial: Activation of Apoptosis-related Receptors on Alveolar Macrophages

Eligibility criteria:
Inclusion Criteria:

        Healthy volunteers

          -  Able and willing to give written informed consent.

          -  Healthy male and female subjects, aged 18-80 years for the initial part and 40-80
             years for the main part, inclusive. Women will be considered for inclusion if they
             are: Not pregnant, as confirmed by pregnancy test (see flow chart), and not nursing.
             Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant,
             including any female who is pre-menarchial or post-menopausal, with documented proof
             of hysterectomy or tubal ligation, or meets clinical criteria for menopause and has
             been amenorrhoeic for more than 1 year prior to the screening visit). Of childbearing
             potential and using a highly effective method of contraception during the entire study
             (vasectomised partner, sexual abstinence - the lifestyle of the female should be such
             that there is complete abstinence from intercourse from two weeks prior to the first
             dose of study medication until at least 72 hours after treatment -, implants,
             injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs) or
             double-barrier methods, i.e. any double combination of IUD, condom with spermicidal
             gel, diaphragm, sponge, and cervical cap).

          -  Normal lung function with Forced Expiratory Volume in 1 second (FEV1) predicted ≥ 80%
             and FEV1/Forced Vital Capacity (FVC) > 70%.

          -  Body mass index between 18 and 32 kg/m2

          -  Ex-smokers since at least 12 months with a smoking history of at least 10 pack years.

          -  Able and willing to give written informed consent

        COPD subjects

          -  Male and female subjects, aged 40-80 years, inclusive. Women will be considered for
             inclusion if they are: Not pregnant, as confirmed by pregnancy test (see flow chart),
             and not nursing. Of non-child bearing potential (i.e. physiologically incapable of
             becoming pregnant, including any female who is pre-menarchial or post-menopausal, with
             documented proof of hysterectomy or tubal ligation, or meets clinical criteria for
             menopause and has been amenorrhoeic for more than 1 year prior to the screening
             visit). Of childbearing potential and using a highly effective method of contraception
             during the entire study (vasectomised partner, sexual abstinence - the lifestyle of
             the female should be such that there is complete abstinence from intercourse from two
             weeks prior to the first dose of study medication until at least 72 hours after
             treatment -, implants, injectables, combined oral contraceptives, hormonal IUDs or
             double-barrier methods, i.e. any double combination of IUD, condom with spermicidal
             gel, diaphragm, sponge, and cervical cap).

          -  Clinical diagnosis of COPD stage II and III

          -  History of chronic cough and sputum production

          -  FEV1/FVC <70% post-bronchodilator at visit 1

          -  FEV1 30-80% of the predicted normal value post-bronchodilator at visit 1

          -  FEV1 >1.5 L

          -  Absence of lung emphysema assessed by pulmonary function measurement at visit 1: Total
             Lung Capacity (TLC) <120% of predicted normal, Residual Volume (RV) <120% of predicted
             normal, Diffusing Capacity for Carbon Monoxide (DLCO) >80%

          -  Ex-smokers since at least 12 months with a smoking history of at least 10 pack years.

          -  Body mass index between 18 and 32 kg/m2.

          -  Able and willing to give written informed consent.

        Exclusion Criteria:

        Healthy volunteers

          -  Past or present disease, which as judged by the investigator, may affect the outcome
             of the study or put the subject at risk because of participation in the study. These
             diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic
             disease, renal disease, haematological disease, neurological disease, psychiatric
             disease, endocrine disease, infectious disease, inflammatory disease or pulmonary
             disease (including but not confined to asthma, tuberculosis, bronchiectasis or cystic
             fibrosis)

          -  Regular intake of any prescribed or over the counter medication. Exceptions include
             paracetamol for pain relief, oral contraceptive medication, hormonal replacement
             therapy, dietary and vitamin supplements

          -  Clinically relevant history of allergy as judged by the investigator

          -  Intolerance against standard medication used during bronchoscopy, e.g. lidocaine,
             midazolam.

          -  Infections of the lower respiratory tract within 6 weeks prior to screening

          -  Infections of the upper respiratory tract within 2 weeks prior to screening

          -  Any clinically relevant abnormal findings in physical examination, clinical chemistry,
             haematology, urinalysis, vital signs, lung function, or ECG at Visit 1, which, in the
             opinion of the investigator, may either put the subject at risk because of
             participation in the study, or may influence the results of the study.

          -  HIV (Type I + Type II), hepatitis B or C, tuberculosis, or Sars-CoV-2 positive or not
             performed at visit 1

          -  Positive drug screen for methadone, cannabis, opiates, cocaine metabolites,
             amphetamines, barbiturates and benzodiazepines at visit 1

          -  History of drug or alcohol abuse

          -  Risk of non-compliance with study procedures

          -  Suspected inability to understand the protocol requirements, instructions and
             study-related restrictions, the nature, scope, and possible consequences of the study

        COPD subjects

          -  Past or present disease other than COPD, which as judged by the investigator, may
             affect the outcome of the study or put the subject at risk because of participation in
             the study. These diseases include, but are not limited to, cardiovascular disease,
             malignancy, hepatic disease, renal disease, haematological disease, neurological
             disease, psychiatric disease, endocrine disease, infectious disease, inflammatory
             disease or pulmonary disease (including but not confined to asthma, tuberculosis,
             bronchiectasis or cystic fibrosis).

          -  Regular intake of any prescribed or over the counter medication, which as judged by
             the investigator, may affect the outcome of the study or put the subject at risk
             because of participation in the study. Explicitly allowed is treatment with
             short-acting beta-2-agonists (SABA)/long-acting beta-2-agonists (LABA)/long-acting
             muscarinic-antagonists (LAMA), paracetamol for pain relief, oral contraceptive
             medication, hormonal replacement therapy, dietary and vitamin supplements. Not allowed
             are inhaled corticosteroids.

          -  Clinically relevant history of allergy as judged by the investigator.

          -  Intolerance against standard medication used during bronchoscopy, e.g. lidocaine,
             midazolam.

          -  Infections of the lower respiratory tract within 6 weeks prior to screening.

          -  Infections of the upper respiratory tract within 2 weeks prior to screening

          -  Exacerbation of COPD (treatment with oral or parenteral antibiotics and/or oral or
             parenteral glucocoterticosteroids (GCS) and/or hospitalization related to COPD) within
             60 days of visit 1.

          -  Any clinically relevant abnormal findings in physical examination, clinical chemistry,
             hematology, urinalysis, vital signs, lung function, or ECG at Visit 1, which, in the
             opinion of the investigator, may either put the subject at risk because of
             participation in the study, or may influence the results of the study.

          -  HIV (Type I + Type II), hepatitis B or C, tuberculosis, or Sars-CoV2 positive or not
             performed at visit 1.

          -  Positive drug screen for methadone, cannabis, opiates, cocaine metabolites,
             amphetamines, barbiturates and benzodiazepines at visit 1.

          -  History of drug or alcohol abuse.

          -  Risk of non-compliance with study procedures.

          -  Suspected inability to understand the protocol requirements, instructions and
             study-related restrictions, the nature, scope, and possible consequences of the study.
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 40 Years old.
Subject must be at most 80 Years

Eligibility (NLI label): Contradiction