Aerosolized GM-CSF

Initial animal studies revealed that aerosolized (but not intraperitoneal) GM-CSF corrected the lung lesions in GM-CSF knock-out mice (68). In humans with iPAP, aerosolized GM-CSF has been used in small series (98-100) and anecdotal case reports (3101). Aerosolized GM-CSF markedly reduced anti-GM-CSF antibodies in three patients with iPAP (98). Inhaled GM-CSF was shown to decrease the amount of autoantibody in BALF and improve pulmonary function in patients with iPAP (98-100). Although GM-CSF appears promising in a subset of patients with moderate-to-severe PAP, many important questions remain unanswered including the optimal dose, duration, and route of administration. Importantly, which patients are candidates for therapy remains unclear. Additionally, markers to predict response to GM-CSF therapy need to be identified. To date, smdies suggest that titers of circulating anti-GM-CSF, a normal LDH level, and GM-CSF-induced eosinophilia predict a higher level of success with GM-CSF (24,74,90,96). 

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Treatment whole lung lavage (WLL) current standard. Subcutaneous or aerosolized GM-CSF promising... 

Reed JA, Ikegami M, Cianciolo ER, et al. Aerosolized GM-CSF ameliorates pulmonary alveolar proteinosis in GM-CSF-deficient mice. Am J Physiol 1999 276(4 pt 1) L556-L563. 

Stampfli MR, Wiley RE, Scott Neigh G, Gajewska BU, Lei XF, Snider DP, Xing Z, Jordana M GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice. J Clin Invest 1998 102 1704-1714. 

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