title: Interstitial pneumonitis as an adverse reaction to mTOR inhibitors.
abstract: BACKGROUND
  mTOR (mammalian target of rapamycin) inhibitors sirolimus and everolimus, used as immunosuppressants in solid organ transplantation, may cause severe adverse effects, such as interstitial pneumonitis. INCIDENCE AND CLINICAL PRESENTATION: The estimated incidence of interstitial pneumonitis is 4-11% although it may be higher. Most reported cases have occurred in renal transplant recipients treated with sirolimus. Clinical presentation is heterogeneous, which makes diagnosis difficult. Abnormalities, such as ground glass opacities, are often found in computerised axial tomography scans of the chest. Physiopathology is not well-known. However, patients with abnormal renal function and those with previous calcineurin inhibitor treatment display a higher incidence. The relationship between pneumonitis and mTOR inhibitor plasma concentrations is not well defined.
  
  
  METHODS
  Drug discontinuation and administration of high doses of corticosteroids seems to be an effective treatment. mTOR inhibitor dose reduction and replacing sirolimus with everolimus are other alternatives, but they are still under discussion.
  
  
  CONCLUSIONS
  Iatrogenic pneumonitis must be suspected when a transplant recipient being treated with mTOR inhibitors presents respiratory symptoms. There is lack of conclusive data on treatment strategies. It appears that everolimus may be tolerated better than sirolimus.
authors.affiliation: Servicio de Farmacia Hospitalaria, Hospital Clínic de Barcelona, Spain. gmolas@clinic.ub.es
authors.forename: Gloria
authors.initials: G
authors.lastname: Molas-Ferrer
authors.forename: Dolors
authors.initials: D
authors.lastname: Soy-Muner
authors.forename: Helena
authors.initials: H
authors.lastname: Anglada-Martínez
authors.forename: Gisela
authors.initials: G
authors.lastname: Riu-Viladoms
authors.forename: Anna
authors.initials: A
authors.lastname: Estefanell-Tejero
authors.forename: Josep
authors.initials: J
authors.lastname: Ribas-Sala
mesh_terms: D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D017563:Lung Diseases, Interstitial / Q000139:chemically induced*; D020123:Sirolimus / Q000009:adverse effects* / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus