[Lung toxicity induced by rapamycin]

C Damas1, A Oliveira, A Morais

  • 1Serviço de Pneumologia, Hospital de São João, Alameda Hernâni Monteiro, 4200-451 Porto.

Insights

Sirolimus can cause drug-induced lung diseases (DILD) in transplant patients, presenting diverse symptoms and HRCT findings. Early drug withdrawal led to significant improvement, suggesting varied sirolimus-related lung injury mechanisms.

Area of Science:

  • Pulmonology
  • Pharmacology
  • Transplantation Medicine

Background:

  • Drug-induced lung diseases (DILD) represent a growing cause of morbidity.
  • Sirolimus, an immunosuppressant, is increasingly used in solid organ transplantation.
  • Pulmonary toxicity is a recognized complication of sirolimus therapy.

Observation:

  • Four transplant recipients (3 male, 1 female; ages 46-71) developed lung issues.
  • Patients presented with fever, dyspnea, and productive cough.
  • HRCT scans revealed diffuse pulmonary infiltrates with basal predominance.

Findings:

  • Bronchoalveolar lavage (BAL) showed lymphocytic alveolitis in 3 cases, with varying CD4/CD8 ratios.
  • Two patients had neutrophilia, and one experienced alveolar hemorrhage.
  • Pulmonary infections were excluded; drug suspension resulted in clinical improvement.

Implications:

  • Sirolimus-induced lung injury can manifest with diverse clinical and BAL findings.
  • These variations may indicate distinct underlying pathophysiological processes.
  • Further research is needed to elucidate the mechanisms of sirolimus pulmonary toxicity.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...