Table 2

Features and ethical issues with the acute cigarette smoke challenge

Features of the model	Ethical issues
Advantages Human model Acute-on-chronic inflammation Serial non-invasive sampling Combined direct measurement of biomarkers and ex vivo stimulation Limited numbers of strictly defined patients Compare with in vivo animal models	All patients must be advised to stop smoking, and offered full clinical, psychological and pharmacological support to carry this out There must be no encouragement for the patient to begin or continue smoking Some frail patients with COPD will have difficulty fasting and refraining from cigarettes for the morning Clinical disease detected through the investigations must be fully treated, regardless of participation in the study
Disadvantages Difficulty recruiting a small number of highly defined patients Need to validate upper versus lower airway inflammation, including tissue biopsies Signal parameters must reliably change after acute cigarette smoke exposure Lung function and CT changes may occur after acute smoke exposure	Some frail patients with COPD will have difficulty fasting and refraining from cigarettes for the morning The patient should not be taking any anti-inflammatory or confounding therapy: therapy must not be withheld

Features of the model

Ethical issues

Advantages

Human model
Acute-on-chronic inflammation
Serial non-invasive sampling
Combined direct measurement of biomarkers and ex vivo stimulation
Limited numbers of strictly defined patients
Compare with in vivo animal models

All patients must be advised to stop smoking, and offered full clinical, psychological and pharmacological support to carry this out
There must be no encouragement for the patient to begin or continue smoking
Some frail patients with COPD will have difficulty fasting and refraining from cigarettes for the morning
Clinical disease detected through the investigations must be fully treated, regardless of participation in the study

Disadvantages

Difficulty recruiting a small number of highly defined patients
Need to validate upper versus lower airway inflammation, including tissue biopsies
Signal parameters must reliably change after acute cigarette smoke exposure
Lung function and CT changes may occur after acute smoke exposure

Some frail patients with COPD will have difficulty fasting and refraining from cigarettes for the morning
The patient should not be taking any anti-inflammatory or confounding therapy: therapy must not be withheld

COPD, chronic obstructive pulmonary disease.