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Mercuric chloride (HgCl2) is extremely toxic to both humans and animals. It could be absorbed via ingestion, inhalation, and skin contact. Exposure to HgCl2 can cause severe health effects, including damages to the gastrointestinal, respiratory, and central nervous systems. The purpose of this work was to explore if carvacrol (CRV) could protect rats lungs from damage caused by HgCl2. Intraperitoneal injections of HgCl2 at a dose of 1.23 mg/kg body weight were given either alone or in conjunction with oral CRV administration at doses of 25 and 50 mg/kg body weight for 7 days. The study included biochemical and histological techniques to examine the lung tissue's oxidative stress, apoptosis, inflammation, and autophagy processes. HgCl2‐induced reductions in GSH levels and antioxidant enzymes (SOD, CAT, and GPx) activity were enhanced by CRV co‐administration. Furthermore, MDA levels were lowered by CRV. The inflammatory mediators NF‐κB, IκB, NLRP3, TNF‐α, IL‐1β, IL6, COX‐2, and iNOS were all reduced by CRV. When exposed to HgCl2, the levels of apoptotic Bax, caspase‐3, Apaf1, p53, caspase‐6, and caspase‐9 increased, but the levels of antiapoptotic Bcl‐2 reduced after CRV treatment. CRV decreased levels of Beclin‐1, LC3A, and LC3B, which in turn decreased HgCl2‐induced autophagy damage. After HgCl2 treatment, higher pathological damage was observed in terms of alveolar septal thickening, congestion, edema, and inflammatory cell infiltration compared to the control group while CRV ameliorated these effects. Consequently, by preventing HgCl2‐induced increases in oxidative stress and the corresponding inflammation, autophagy, apoptosis, and disturbance of tissue integrity in lung tissues, CRV might be seen as a useful therapeutic alternative. [ABSTRACT FROM AUTHOR]

Lead acetate (PbAc) is a compound that produces toxicity in many tissues after exposure. Sinapic acid (SNP) possesses many biological and pharmacological properties. This study aimed to investigate the efficacy of SNP on the toxicity of PbAc in lung tissue. PbAc was administered orally at 30 mg/kg and SNP at 5 or 10 mg/kg for 7 days. Biochemical, genetic, and histological methods were used to investigate inflammatory, apoptotic, endoplasmic reticulum stress, and oxidative stress damage levels in lung tissue. SNP administration induced PbAc‐reduced antioxidant (GSH, SOD, CAT, and GPx) and expression of HO‐1 in lung tissue. It also reduced MDA, induced by PbAc, and thus alleviated oxidative stress. SNP decreased the inflammatory markers NF‐κB, TNF‐α and IL‐1β levels induced by PbAc in lung tissue and exhibited anti‐inflammatory effect. PbAc increased apoptotic Bax, Apaf‐1, and Caspase‐3 mRNA transcription levels and decreased anti‐apoptotic Bcl‐2 in lung tissues. SNP decreased apoptotic damage by reversing this situation. On the other hand, SNP regulated these markers and brought them closer to the levels of the control group. PbAc caused prolonged ER stress by increasing the levels of ATF6, PERK, IRE1α, GRP78 and this activity was stopped and tended to retreat with SNP. After evaluating all the data, While PbAc caused toxic damage in lung tissue, SNP showed a protective effect by reducing this damage. [ABSTRACT FROM AUTHOR]

Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor‐intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein‐1 (MCP‐1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome‐wide RNA‐seq expression patterns revealed that inflammatory and immune response‐related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine‐cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP‐1 was time‐dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method. [ABSTRACT FROM AUTHOR]

Objectives: Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) have shown remarkable clinical activity in patients with non‐small‐cell lung cancer (NSCLC). However, pneumonitis is a serious side effect of ALK TKIs in NSCLC patients. In this meta‐analysis, we aimed to determine the incidence of ALK‐TKI‐associated pneumonitis. Materials and Methods: We searched electronic databases to identify relevant studies published until August 2022. The incidence of pneumonitis was calculated using a fixed‐effects model when no substantial heterogeneity was observed. Otherwise, a random‐effects model was used. Subgroup analyses of different treatment groups were performed. Statistical analyses were conducted using STATA 17.0. Results: Twenty‐six clinical trials involving 4752 patients were eligible for analysis. All‐grade pneumonitis incidence was 2.92% (95% confidence interval [CI]: 1.79%–4.27%), high‐grade (Grade 3–4) pneumonitis incidence was 1.42% (95% CI: 0.84%–2.12%) and Grade 5 pneumonitis incidence was 0.09% (95% CI: 0.00%–0.28%). The subgroup analysis showed that brigatinib was associated with the highest incidence of both all‐grade and high‐grade pneumonitis (7.09% and 3.06%, respectively). ALK TKI treatment after chemotherapy was associated with a higher incidence of all‐grade and high‐grade pneumonitis than first‐line ALK TKI treatment (7.73% vs. 2.26% and 3.64% vs. 1.26%, respectively). Cohorts from Japanese trials had a higher incidence of all‐grade and high‐grade pneumonitis. Conclusion: Our study provides precise data on the incidence of pneumonitis in patients receiving treatment with ALK TKIs. Overall, ALK TKIs have tolerable pulmonary toxicity. Early pneumonitis identification and treatment are required to prevent further deterioration in patients receiving treatment with brigatinib and in those who received prior chemotherapy, particularly in the Japanese population. [ABSTRACT FROM AUTHOR]

The detection of high levels of microplastics in indoor and outdoor air has increased concerns regarding its toxic effects on the respiratory system. They are not easily degradable and can be deposited deep in the lungs. Although several studies have reported inhalation toxicities of microplastics, they are still controversial due to a lack of evidence. Herein, we evaluated the inhalation toxicities of three differently charged polystyrene microplastics (PS‐MPs), the most abundant microplastics in the air. Cytotoxicity and ROS generation were evaluated using WST‐1 and DCF‐DA assays, respectively. To evaluate the toxic effects on the lung, inflammatory responses were analyzed after repeated exposure to the PS‐MPs through intratracheal instillation. To explore the mechanism of toxicity, autophagy and ER stress‐associated proteins were analyzed. Only the positively charged PS‐MPs (NH2‐PS‐MPs) showed cytotoxicity and increased ROS generation in BEAS‐2B cells. Similarly, only NH2‐PS‐MPs significantly increased the expression and secretion of the pro‐inflammatory cytokine IL‐β in the animal experiments. The expression of ER stress proteins indicated that NH2‐PS‐MPs increased ER stress via PERK‐EIF2α and ATF4‐CHOP pathways. Moreover, accumulation of NH2‐PS‐MPs in lysosomes and deformity of the nucleus were observed in BEAS‐2B cells with autophagy induction. Taken together, our results demonstrated that NH2‐PS‐MPs induced autophagic cell death in bronchial epithelial cells, leading to inflammatory responses in the lungs. These results suggest that repeated inhalation of microplastics can result in inflammatory responses in the lung through cellular damage of lung epithelial cells, and that inhalation microplastics should be monitored to reduce inhalation health risks. [ABSTRACT FROM AUTHOR]

Cypermethrin (CYP), a type II synthetic pyrethroid, is the most widely used insecticide worldwide. Inhalation of it may cause side effects. This study is aimed to examine potential protection of quercetin (QUE) which is a well‐known antioxidant in CYP‐induced lung toxicity. Accordingly, 35 Spraque Dawley male rats were divided into five equal groups as follows: I‐Control group, II‐QUE group (50 mg/kg/b.w. QUE), III‐CYP group (25 mg/kg/b.w. CYP), IV‐CYP + QUE 25 (25 mg/kg/b.w. CYP + 25 mg/kg/b.w. QUE), V‐CYP + QUE (25 mg/kg/b.w. CYP + 50 mg/kg/b.w. QUE) were treated with oral gavage throughout 28 days. CYP intoxication was associated with increased malondialdehyde level while glutathione concentration, activities of glutathione peroxidase, superoxide dismutase, and catalase reduced. CYP adminisitration caused of apoptosis in the lung by up‐regulating caspase‐3 and Bax levels and down‐regulating Bcl‐2. CYP also caused of endoplasmic reticulum (ER) stress by increasing mRNA transcript levels of PERK, IRE1, ATF6, and GRP78. Additionally, it was observed that CYP administration activated IL‐6/JAK2/STAT3/MAPK14 signaling pathway and levels of IL‐1β, NF‐κB, TNF‐α, and iNOS in the lung tissue. Therefore, it was determined that CYP administration triggered autophagy by upregulating LC3A and LC3B mRNA transcript levels. Moreover, the protein levels of NF‐κB, caspase‐3, Bax, Bcl‐2, and cytochorme‐c were examined by Western blot analysis. However, co‐treatment with QUE at a dose of 25 and 50 mg/kg considerably protective oxidative stress, inflammation, apoptosis, ER stress, autophagy, and IL‐6/JAK2/STAT3/MAPK14 signaling pathway in lung tissue. Overall, the findings of this study suggest that lung damage associated with CYP toxicity could be protected by QUE administration. [ABSTRACT FROM AUTHOR]

Acrylamide (ACR) has genotoxic, neurotoxic, and carcinogenic effects. From past to present, various plants or their products have been used for therapeutic purposes such as morin. It was aimed to detect possible protective effects of morin vs ACR‐induced lung toxicity. The rats, treated with ACR alone or with morin for 10 consecutive days, were included in the study. A broad variety of biomarkers related to oxidative stress, apoptosis, autophagy, and inflammatory responses were evaluated. ACR increased malondialdehyde (MDA), tumor necrosis factor‐alpha (TNF‐α), cyclooxygenase‐2 (COX‐2), nuclear factor kappa‐B (NF‐κB), Beclin‐1, IL‐1β, bcl‐2 associated X protein (Bax), caspase‐3, light chain 3‐A (LC3‐A), and light chain 3‐B (LC3‐B) levels but reduced mammalian target of rapamycin (mTOR), b‐cell lymphoma‐2 (Bcl‐2), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione (GSH) in lung tissues. The morin had effects on the level of these molecules in a way that is opposite to ACR. While ACR‐induced oxidative stress, apoptotic, autophagic, inflammatory responses, and may cause pulmonary dysfunction, the morin reduced ACR‐induced lung damage. Practical applications: ACR is a toxic chemical produced by frying, baking, roasting, or grilling foods with high starch content and has genotoxic, neurotoxic, and carcinogenic effects. As an antioxidant compound, the morin is obtained from plants or their products. It was aimed to detect possible protective effects of morin against ACR‐induced lung toxicity. It was detected that ACR‐induced oxidative stress, apoptotic, autophagic, inflammatory responses, and may cause pulmonary dysfunction, but the morin reduced ACR‐induced lung damage. [ABSTRACT FROM AUTHOR]

Pulmonary toxicity is documented in long‐term survivors of allogeneic BMT. No studies have specifically evaluated late pulmonary symptomatology in these patients. 85 long‐term pediatric survivors were sent a validated questionnaire of pulmonary symptomatology. Demographic and clinical data were retrospectively collected from the respondents medical records. Response rate was 52.9%. Mean follow‐up post‐BMT of those who responded was 12.3 years. Mean pulmonary symptom scores were low (0.78). There was no significant difference in symptoms between patients who underwent MA conditioning with or without TBI. These results are reassuring that long‐term survivors of pediatric BMT have few respiratory symptoms which do not impact on activities of daily living. [ABSTRACT FROM AUTHOR]

The primary objective is to evaluate the potential dosimetric gains of performing functional avoidance‐based proton treatment planning using 4DCT derived ventilation imaging. 4DCT data of 31 patients from a prospective functional avoidance clinical trial were evaluated with intensity modulated proton therapy (IMPT) plans and compared with clinical volumetric modulated arc therapy (VMAT) plans. Dosimetric parameters were compared between standard and functional plans with IMPT and VMAT with one‐way analysis of variance and post hoc paired student t‐test. Normal Tissue Complication Probability (NTCP) models were employed to estimate the risk of two toxicity endpoints for healthy lung tissues. Dose degradation due to proton motion interplay effect was evaluated. Functional IMPT plans led to significant dose reduction to functional lung structures when compared with functional VMAT without significant dose increase to Organ at Risk (OAR) structures. When interplay effect is considered, no significant dose degradation was observed for the OARs or the clinical target volume (CTV) volumes for functional IMPT. Using fV20 as the dose metric and Grade 2+ pneumonitis as toxicity endpoint, there is a mean 5.7% reduction in Grade 2+ RP with the functional IMPT and as high as 26% in reduction for individual patient when compared to the standard IMPT planning. Functional IMPT was able to spare healthy lung tissue to avoid excess dose to normal structures while maintaining satisfying target coverage. NTCP calculation also shows that the risk of pulmonary complications can be further reduced with functional based IMPT. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiotherapy (SBRT) is the standard care for inoperable early stage non‐small cell lung cancer (NSCLC). The purpose of our study was to investigate whether a prediction model based on cone‐beam CT (CBCT) plus pretreatment CT radiomics features could improve the prediction of tumor control and lung toxicity after SBRT in comparison to a model based on pretreatment CT radiomics features alone. Methods: A total of 34 cases of stage I NSCLC patients who received SBRT were included in the study. The pretreatment planning CT and serial CBCT radiomics features were analyzed using the imaging biomarker explorer (IBEX) software platform. Multivariate logistic regression was conducted for the association between progression‐free survival (PFS), lung toxicity and features. The predictive capabilities of the models based on CBCT and CT features were compared using receiver operating characteristic (ROC) curves. Results: Five CBCT features and two planning CT features were correlated with disease progression. Six CBCT features and two planning CT features were related to lung injury. The ROC curves indicated that the model based on the CBCT plus planning CT features might be better than the model based on the planning CT features in predicting lung injury. The other ROC curves indicated that the model based on the planning CT features was similar to the model based on the CBCT plus planning CT features in predicting disease progression. Conclusions: Both pretreatment CT and CBCT radiomics features could predict disease progression and lung injury. A model with CBCT plus pretreatment CT radiomics features might improve the prediction of lung toxicity in comparison with a model with pretreatment CT features alone. Key points: Significant findings of the study: A model with cone‐beam CT radiomics features plus pre‐treatment CT radiomics features might improve the prediction of lung toxicity after SBRT in stage I NSCLC patients.What this study adds: In the prediction of PFS and lung toxicity in early‐stage NSCLC patients treated with SBRT, CBCT radiomics could be another effective method. [ABSTRACT FROM AUTHOR]

Resistance to radiotherapy and to EGFR tyrosine kinase inhibitors (EGFR‐TKIs), as well as therapy‐related lung toxicity, are serious problems in the treatment of lung cancer. NF‐κB has been reported to be associated with radioresistance. Therefore, we evaluated its effects on sensitivity to irradiation and to EGFR‐TKIs; irradiation‐induced lung toxicity; and the effects of irradiation on sensitivity to EGFR‐TKIs. We used IKKβ inhibitor IMD 0354 or p65 depletion to explore their effects on sensitivity to irradiation and to EGFR‐TKIs in vitro and in vivo. We evaluated the efficacy of IMD 0354 in a radiation‐induced pulmonary‐fibrosis mouse model. Irradiation enhanced activation and expression of MET and therefore suppressed the sensitivity of lung cancer cells to irradiation or EGFR‐TKIs. Inhibition of NF‐κB by IMD 0354 or by p65 depletion reversed irradiation‐induced MET activation and increased the sensitivity of lung cancer cells to irradiation, to EGFR‐TKIs and to the combination thereof in vitro and in vivo. In addition, IMD 0354 significantly reduced lung toxicity in a murine model of irradiation‐induced pneumonia and lung fibrosis. These findings indicated that NF‐κB inhibition can improve sensitivity to irradiation and to EGFR‐TKIs and can decrease irradiation‐inducedlung toxicity in lung cancer. What's new? The efficacy of lung cancer treatment is limited by various factors, including resistance to radiotherapy and epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs). The mechanisms underlying therapeutic resistance, however, remain unclear. In this study, investigation of the effects on treatment sensitivity of NF‐κB, a factor previously associated with radioresistance in cancer cells, shows that irradiation reduces lung cancer cell susceptibility to EGFR‐TKIs. This effect was overcome by NF‐κB inhibition, which increased radiosensitivity via effects on MET signaling. The findings indicate that irradiation‐induced NF‐κB activation and subsequent MET upregulation serve a critical role in therapeutic resistance in lung cancer. [ABSTRACT FROM AUTHOR]

Benzo(a)pyrene [B(a)P] is a well-known carcinogen present in the environment. In this study, we evaluated the protective potential of methanolic bark extract of Acacia catechu Willd. (MEBA) against the lung toxicity induced by B(a)P in Swiss albino mice. To determine the protective efficacy of MEBA, it was orally administered to the mice at two doses (200 and 400 mg/kg body weight) once daily for 7 days. Mice were also exposed (orally) to B(a)P at a dose of 125 mg/kg body weight on 7th day. Administration of B(a)P increased the activities of toxicity markers such as LDH, LPO, and XO with a subsequent decrease in the activities of tissue anti-oxidant armory (CAT, SOD, GST, GPx, GR, QR, and GSH). It also caused activation of the apoptotic and inflammatory pathway by upregulation of TNF-α, NF-kB, COX-2, p53, bax, caspase-3, and downregulating Bcl-2. Pretreatment with MEBA at two different doses (200 and 400 mg/kg body weight) significantly ameliorates B(a)P-induced increased toxicity markers and activities of detoxifying enzymes along with the levels of glutathione content. It also significantly attenuated expression of apoptotic and inflammatory markers in the lungs. Histological results further confirmed the protective role of MEBA against B(a)P-induced lung toxicity. The results indicate that MEBA may be beneficial in ameliorating the B(a)P-induced oxidative stress, inflammation, and apoptosis in the lungs of mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1566-1577, 2017. [ABSTRACT FROM AUTHOR]

Background and Purpose Breast cancer patients exposed to doses of radiation after radiotherapy could develop toxicity to lung. Lung ultrasound ( LUS) is able to detect interstitial lung disease by the evaluation of B-lines. The aim of our study was to assess the number of B-lines to diagnose lung involvement after chest radiotherapy. Materials and Methods We measured LUS B-lines in the treated and contralateral lung of 20 breast cancer patients, 1-3 months after the end of radiotherapy and 1 year after previous LUS. The sum of the B-lines number in the 72 sites on anterior and posterior chest yielded a global B-lines score. Results B-lines were more numerous in treated (median: 21; 1st-3rd quartiles: 11-31) versus untreated hemithorax (median: 3; 1st-3rd quartiles: 1-5) in both examination at T1-3 months (Kolmogorov-Smirnov test P < 0.001) and T1 year (median: 21; 1st-3rd quartiles: 12-28 vs. median: 4; 1st-3rd quartiles: 1-10; Kolmogorov-Smirnov test P < 0.01). Within the treated hemithorax, B-lines were more frequent in the anterior than in the posterior chest in both examination at T1-3 months (Kolmogorov-Smirnov test: P < 0.0001) and T1 year (Kolmogorov-Smirnov test: P < 0.01). Abnormal scores (B-lines>5) were present in 17/20 treated versus 7/20 untreated hemithoraxes (85.0 vs. 35.0%, P < 0.01) in the first LUS and likewise in 16/17 treated versus 7/17 in untreated hemithorax (94.1% vs. 41.2%, P < 0.01) after 1-year follow-up. Conclusion Among women receiving radiotherapy after breast cancer, B-lines are present predominantly in the irradiated lung. These data suggest that B-lines by LUS could provide, at a subclinical stage, a radiation-free biomarker of radiotherapy-induced lung damage. [ABSTRACT FROM AUTHOR]

The mechanisms involved in bleomycin-induced lung toxicity have not been fully understood to date. This work aimed to compare the proteome profiling of bleomycin-induced lung toxicity by using 2D-nano-LC-MS/MS and spectral counting. By comparing the spectral counts of identified proteins between control and bleomycin-treated groups, we noted that 102 proteins were upregulated and 28 proteins were downregulated in the bleomycin-treated group. Among these differently expressed proteins, five proteins were chosen for validation by Western blot analysis. The levels of these five proteins were consistent with proteomic results. These potential mediators can facilitate the translation of the underlying mechanisms of bleomycin-induced lung toxicity to molecular targets in the clinical arena. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiation therapy (SBRT) is becoming the standard of care for early stage nonoperable lung cancers. Accurate dose-response modeling is challenging for SBRT because of the decreased number of clinical toxicity events. As a surrogate for a clinical toxicity endpoint, studies have proposed to use radiographic changes in follow up computed tomography (CT) scans to evaluate lung SBRT normal tissue effects. The purpose of the current study was to use local fibrotic lung regions to spatially and dosimetrically evaluate lung changes in patients that underwent SBRT. Methods: Forty seven SBRT patients treated at our institution from 2003 to 2009 were used for the current study. Our patient cohort had a total of 148 follow up CT scans ranging from 3 to 48 months post-therapy. Post-treatment scans were binned into intervals of 3, 6, 12, 18, 24, 30, and 36 months after the completion of treatment. Deformable image registration was used to align the follow up CT scans with the pretreatment CT and dose distribution. Areas of visible fibrotic changes were contoured. The centroid of each gross tumor volume (GTV) and contoured fibrosis volume was calculated and the fibrosis volume location and movement (magnitude and direction) relative to the GTV and 30 Gy isodose centroid were analyzed. To perform a dose-response analysis, each voxel in the fibrosis volume was sorted into 10 Gy dose bins and the average CT number value for each dose bin was calculated. Dose-response curves were generated by plotting the CT number as a function of dose bin and time posttherapy. Results: Both fibrosis and GTV centroids were concentrated in the upper third of the lung. The average radial movement of fibrosis centroids relative to the GTV centroids was 2.6 cm with movement greater than 5 cm occurring in 11% of patients. Evaluating dose-response curves revealed an overall trend of increasing CT number as a function of dose. The authors observed a CT number plateau at doses ranging from 30 to 50 Gy for the 3, 6, and 12 months posttherapy time points. There was no evident plateau for the dose-response curves generated using data from the 18, 24, 30, and 36 months posttherapy time points. Conclusions: Regions of local fibrotic lung changes in patients that underwent SBRT were evaluated spatially and dosimetrically. The authors found that the average fibrosis movement was 2.6 cm with movement greater than 5 cm possible. Evaluating dose-response curves revealed an overall trend of increasing CT number as a function of dose. Furthermore, our dose-response data also suggest that one of the possible explanations of the CT number plateau effect may be the time posttherapy of the acquired data. Understanding normal tissue dose-response is important for reducing toxicity after SBRT, especially in cases where larger tumors are treated. The methods presented in the current work build on prior quantitative studies and further enhance the understanding of normal lung dose-response after SBRT. [ABSTRACT FROM AUTHOR]

The article reports that six patients with acute myeloid leukaemia were treated with intermediate to high-dose cytosine-arabinoside (Ara-C) (HDAC) and developed a new pattern of drug-related pulmonary infiltrates. The patients revealed centrilobular micronodular pulmonary infiltrates during the course of an infection workup for febrile neutropenia following induction chemotherapy combining anthracycline and intermediate to high-dose Ara-C.

Sirolimus is a potent immunosuppressive agent used with increasing frequency in solid organ transplantation (SOT). However, it has been associated with rare but devastating pulmonary toxicity. We describe a case of pulmonary toxicity associated with the use of sirolimus in a 64-yr-old heart transplant recipient. We also review all reported cases of sirolimus-associated lung toxicity among SOT recipients in an effort to better understand the pathophysiology, risk factors, and outcomes of this rare but serious complication. A total of 64 cases have been reported since January 2000 including the present case. These consisted of 52 kidney, four lung, three liver, three heart, one heart–lung and one islet cell transplants. In most cases, patients presented with a constellation of symptoms consisting of fever, dyspnea, fatigue, cough, and occasionally hemoptysis. Although the risk factors for this association have not been clearly established, high dose, late exposure to the drug and male gender have been noticed among most. In almost all of the reported cases, sirolimus was added later in the course of immunosuppressive therapy, usually in an effort to attenuate the nephrotoxic effects of a previous regimen containing a calcineurin inhibitor. There were three deaths (4.8%) among 62 patients with known status at follow up; all deaths were among heart transplant recipients. Most patients (95%) resolved their clinical and radiographic findings with discontinuation or dose-reduction of the drug. Sirolimus-induced pulmonary toxicity is a rare but serious entity that should be considered in the differential diagnosis of a transplant recipient presenting with respiratory compromise. Dose-reduction or discontinuation of the drug can be life saving. [ABSTRACT FROM AUTHOR]