**Core Concept**
The systemic adverse effects of long-term inhaled corticosteroids (ICS) are primarily due to their absorption from the lungs into the systemic circulation, where they can exert glucocorticoid effects on various tissues. This is a concern with high doses of ICS, as it may lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis, growth suppression in children, and other systemic effects.

**Why the Correct Answer is Right**
Inhaled corticosteroids have a relatively low oral bioavailability due to first-pass metabolism in the liver. However, with high doses, the amount absorbed into the systemic circulation increases, leading to significant systemic exposure. The threshold for systemic adverse effects is generally considered to be around 800-1000 mcg/day of beclomethasone dipropionate or equivalent doses of other ICS. This is because at doses above this threshold, the systemic exposure exceeds the liver's ability to metabolize the drug, leading to increased systemic effects.

**Why Each Wrong Option is Incorrect**
**Option A:** There is no established threshold for systemic adverse effects below 400 mcg/day of beclomethasone dipropionate. In fact, most studies suggest that doses below 800 mcg/day are generally safe in terms of systemic effects.
**Option B:** Doses of 200 mcg/day of beclomethasone dipropionate are commonly used in the treatment of mild asthma and are not associated with significant systemic adverse effects.
**Option C:** There is no specific dose of fluticasone propionate that is associated with systemic adverse effects. However, high doses (e.g., >1000 mcg/day) may be more likely to cause systemic effects due to its high potency and bioavailability.

**Clinical Pearl / High-Yield Fact**
When prescribing inhaled corticosteroids, it's essential to use the lowest effective dose for the shortest duration necessary to control symptoms, as high doses and prolonged use can increase the risk of systemic adverse effects. Regular monitoring of lung function and bone density may be necessary in patients on high doses of ICS.

**Correct Answer: D. 800-1000 mcg/day**