Abstract: Prolyl endopeptidase (PE) activity in lung samples is detected by contacting the lung sample with a probe comprising a —P—X— (or —X—P—, —P—X—P—) PE recognition site, wherein P is a prolyl bioisostere, X is a residue that is not a prolyl bioisostere or is a prolyl bioisostere flanked on each side by a residue that is not a prolyl bioisostere, and “-” is an amide bond, under conditions wherein PE activity of the sample specifically hydrolyzes an amide bond of the recognition site to generate an optical signal; and (b) detecting the signal.