sirolimus and Cough

The mammalian target of rapamycin (mTOR) inhibitor class of drugs represents the newest addition to the armamentarium of therapies for hormonally driven breast cancer. It has recently been shown that the addition of mTOR inhibitor everolimus to aromatase inhibitors in hormone receptor-positive breast cancers improves progression-free survival. However, a clinically significant toxicity associated with this class of drugs is the development of noninfectious pneumonitis (NIP). Although generally mild and manageable, everolimus-induced NIP requires prompt diagnosis and management. This article will provide a brief overview of data relating to dysregulation of the phosphatidylinositol-3-kinase/protein kinase B/mTOR pathway in breast cancer; review the literature relating to the efficacy and safety of mTOR inhibitors in breast cancer; and evaluate the incidence, severity, and optimal management of mTOR inhibitor-related NIP in breast cancer.

Topics: Antineoplastic Agents; Breast Neoplasms; Cough; Dyspnea; Elafin; Everolimus; Female; Humans; Incidence; Pneumonia; Proto-Oncogene Proteins c-akt; Severity of Illness Index; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases

Topics: Chest Pain; Cough; Diagnosis, Differential; Dyspnea; Female; Humans; Lung; Lung Diseases, Fungal; Lung Neoplasms; Lymphangioleiomyomatosis; Magnetic Resonance Imaging; Pneumonia, Bacterial; Pneumothorax; Radiography, Thoracic; Risk Factors; Shock; Sirolimus; Thoracostomy; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Young Adult

Topics: Aged; Ascites; Cough; Drug Therapy, Combination; Erdheim-Chester Disease; Female; Fever; Glucocorticoids; Humans; Immunosuppressive Agents; Middle Aged; Prednisolone; Radionuclide Imaging; Sirolimus; Tomography, X-Ray Computed

Bronchiectasis is characterized by abnormal, permanent and irreversible dilatation of the bronchi, usually responsible for daily symptoms and frequent respiratory complications. Many causes have been identified, but only limited data are available concerning the association between bronchiectasis and renal transplantation.. We conducted a retrospective multicenter study of cases of bronchiectasis diagnosed after renal transplantation in 14 renal transplantation departments (French SPIESSER group). Demographic, clinical, laboratory and CT scan data were collected.. Forty-six patients were included (mean age 58.2 years, 52.2 % men). Autosomal dominant polycystic kidney disease (32.6 %) was the main underlying renal disease. Chronic cough and sputum (50.0 %) were the major symptoms leading to chest CT scan. Mean duration of symptoms before diagnosis was 1.5 years [0-12.1 years]. Microorganisms were identified in 22 patients, predominantly Haemophilus influenzae. Hypogammaglobulinemia was observed in 46.9 % patients. Bronchiectasis was usually extensive (84.8 %). The total bronchiectasis score was 7.4 ± 5.5 with a significant gradient from apex to bases. Many patients remained symptomatic (43.5 %) and/or presented recurrent respiratory tract infections (37.0 %) during follow-up. Six deaths (13 %) occurred during follow-up, but none were attributable to bronchiectasis.. These results highlight that the diagnosis of bronchiectasis should be considered in patients with de novo respiratory symptoms after renal transplantation. Further studies are needed to more clearly understand the mechanisms underlying bronchiectasis in this setting.

Topics: Adult; Agammaglobulinemia; Aged; Aged, 80 and over; Azathioprine; Bronchiectasis; Chronic Disease; Cough; Cyclosporine; Everolimus; Female; Forced Expiratory Volume; Graft Rejection; Haemophilus Infections; Haemophilus influenzae; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Polycystic Kidney, Autosomal Dominant; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Rituximab; Sirolimus; Tacrolimus; Tomography, X-Ray Computed; Vital Capacity; Young Adult

Topics: Cough; Dyspnea; Forced Expiratory Volume; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Sirolimus; Surgical Stapling; Surgical Wound Dehiscence; Sutures

Sirolimus-associated pulmonary problems are rare but life threatening. Pulmonary problems due to sirolimus treatment are interstitial pneumonitis, bronchiolitis obliterans organizing pneumonia (BOOP), and alveolar hemorrhage. We present a case of sirolimus-related cough in the absence of any pulmonary radiological findings. A 55-year-old man with a history of 4 years of hemodialysis therapy because of end-stage renal disease of unknown etiology underwent cadaveric renal transplantation in June 2006. Three days following the initiation of sirolimus therapy he complained of dry cough and fever. There were no clinical or laboratory findings compatible with specific pulmonary disease. After switching sirolimus to tacrolimus, the cough improved within 1-2 days and resolved in 5 days. Sirolimus should be considered in the differential diagnosis of pulmonary problems in the early posttransplantation period even in the absence of radiological findings.

Topics: Cough; Cryptogenic Organizing Pneumonia; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Sirolimus; Tacrolimus; Treatment Outcome

Topics: Anti-Inflammatory Agents; Body Temperature; Bronchoalveolar Lavage Fluid; Bronchoscopy; Coronary Artery Bypass; Cough; Cyclosporine; Diabetic Nephropathies; Diagnosis, Differential; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Lung Diseases, Interstitial; Middle Aged; Prednisone; Radiography, Thoracic; Risk Factors; Sirolimus; Tomography, X-Ray Computed; Xenobiotics