“…This classification has had a great impact on patient psychopathology, response to treatment and prognosis. 6 New hypotheses for PD have advanced enormously in the last decades due to the possibility of reproducing PAs in a safe and controlled environment. The carbon dioxide (CO 2 ) challenge has been regarded as a safe and noninvasive method to provoke PAs in PD patients in preclinical and clinical research settings, and has enabled investigators to: analyze sensitivity to hypercapnia in PD, assessing the validity of Klein's suffocation alarm theory; discriminate the respiratory (R-PD) and non-respiratory (nR-PD) subtypes of PD according to patient sensitivity to hypercapnia; test the sensitivity of healthy relatives of PD patients to the CO 2 challenge; verify the ability of drugs with known pharmacokinetics to prevent, eliminate, or reduce CO 2 sensitivity in R-PDs, shedding light on the neural mechanisms of PAs and potential treatment options for PD; assess the efficacy of non-drug treatments, such as physical exercise, in preventing PAs caused by hypercapnia; and develop genetic screening for CO 2 -sensitive PD.…”