Pattern Of Lung Injury Research Articles

Radiologic Review With Pathology Correlation of E-Cigarette or Vaping Product Use-associated Lung Injury.

More than 2000 cases of vaping-associated lung injury have been reported in a recent outbreak, including >40 deaths. Although chest imaging is integral in the evaluation of these patients and is often abnormal, the spectrum of findings and the role of imaging in the diagnosis are not widely appreciated. The aim of this review is to highlight the imaging findings of vaping-associated lung injury. Basilar-predominant ground-glass opacities and/or consolidations, often with areas of subpleural or lobular sparing, are the most common pattern, and many other patterns are known to occur. Radiologists are encouraged to become familiar with the different imaging patterns of vaping-associated lung injury. The diagnosis should be considered in patients who have vaped within 90 days of onset of symptoms and present with bilateral lung opacities.

Radiologic, Pathologic, Clinical, and Physiologic Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): Evolving Knowledge and Remaining Questions.

Proposed as a safer alternative to smoking, the use of electronic cigarettes has not proven to be innocuous. With numerous deaths, there is an increasing degree of public interest in understanding the symptoms, imaging appearances, causes of, and treatment of electronic cigarette or vaping product use-associated lung injury (EVALI). Patients with EVALI typically have a nonspecific clinical presentation characterized by a combination of respiratory, gastrointestinal, and constitutional symptoms. EVALI is a diagnosis of exclusion; the patient must elicit a history of recent vaping within 90 days, other etiologies must be eliminated, and chest imaging findings must be abnormal. Chest CT findings in EVALI most commonly show a pattern of acute lung injury on the spectrum of organizing pneumonia and diffuse alveolar damage. The pathologic pattern found depends on when in the evolution of the disease process the biopsy sample is taken. Other less common forms of lung injury, including acute eosinophilic pneumonia and diffuse alveolar hemorrhage, have also been reported. Radiologists and pathologists help play an important role in the evaluation of patients suspected of having EVALI. Accurate and rapid identification may decrease morbidity and mortality by allowing for aggressive clinical management and glucocorticoid administration, which have been shown to decrease the severity of lung injury in some patients. In this review, the authors summarize the current state of the art for the imaging and pathologic findings of this disorder and outline a few of the major questions that remain to be answered.

Radiation-induced lung injury patterns and the misdiagnosis after SBRT of lung cancer

PurposeTo analyze radiation-induced lung injury (RIL) after stereotactic body radiotherapy (SBRT) of lung cancer and the subsequent clinical problems. Methods106 lung cancer patients treated with SBRT were included, their computed tomography (CT) scans were reviewed. Late injury pattern was classified by Koening’s, radiologist’ diagnosis reports for RIL was reviewed. Logistic regression was used to analyze the predictive model of injury pattern, which was also validated by ROC curve. ResultsRadiographic late injury within at least 6 months after SBRT was concluded. The majority of late RIL was mass-like pattern, not the modified conventional pattern. 36.8% patients showed acute injury, which trend to occur late lung injury earlier than patients who were not found acute injury (p = 0.0185). 24.5% RIL cases were misdiagnosed to tumor progression by radiologists. Most misdiagnosis occurred among mass-like pattern. Per fraction dose (p < 0.0001), prescription isodose line (p = 0.027) and age (p = 0.089) trend to associate with the occurrence of mass-like injury pattern. Nomogram was established based on these parameters, ROC curve showed that area under the ROC curve (AUC) of the nomogram was 0.767 (95% CI = 0.677-0.857), which was better than any factors along. ConclusionSBRT for lung cancer patients was safe, the majority of late RIL was mass-like pattern. This injury was difficult to be distinguished from tumor progression, which leaded to misdiagnosis of 24.5% patients receiving SBRT. A nomogram based on age, per fraction dose and the prescription isodose line may assist the diagnosis in clinical practice.

Lung Biopsy Findings in Severe Pulmonary Illness Associated With E-Cigarette Use (Vaping).

The aim of this report is to describe the lung biopsy findings in vaping-associated pulmonary illness. Lung biopsies from eight patients with vaping-associated pulmonary illness were reviewed. The biopsies were from eight men (aged 19-61 years) with respiratory symptoms following e-cigarette use (vaping). Workup for infection was negative in all cases, and there was no evidence for other etiologies. Imaging showed diffuse bilateral ground-glass opacities in all patients. Most recovered with corticosteroid therapy, while one died. Lung biopsies (seven transbronchial, one surgical) showed acute lung injury, including organizing pneumonia and/or diffuse alveolar damage. Common features were fibroblast plugs, hyaline membranes, fibrinous exudates, type 2 pneumocyte hyperplasia, and interstitial organization. Some cases featured a sparse interstitial chronic inflammatory infiltrate. Although macrophages were present within the airspaces in all cases, this feature was not prominent, and findings typical of exogenous lipoid pneumonia were absent. The histopathology of acute pulmonary illness related to e-cigarette use (vaping) is characterized by acute lung injury patterns, supporting the contention that vaping can cause severe lung damage.

Imaging Findings of Vaping-Associated Lung Injury.

To listen to the podcast associated with this article, please select one of the following: iTunes or Google Play. OBJECTIVE. E-cigarettes are devices that aerosolize nicotine- or cannabis-based concentrates mixed with other solvents and have been marketed as an alternative to cigarettes. E-cigarette use, or vaping, is increasingly popular but has not been proven to be an innocuous substitute for traditional smoking. Several patterns of vaping-associated inhalational lung injuries have been reported in the past few years. This article reviews many of the imaging patterns that have been encountered in association with e-cigarette use. CONCLUSION. E-cigarette use is associated with a range of lung injury patterns that have only recently been recognized as use of these products continues to rise. When the radiologist sees one of these patterns of lung injury, it is important to raise the possibility of vaping-induced lung injury because cessation of vaping is an important step in treatment.

1455P - Radiation-induced lung injury and misdiagnosis rate after SBRT

BackgroundPreviously, studies showed the distribution of radiation-induced lung injury (RIL) pattern after stereotactic body radiotherapy (SBRT) of non-small cell lung cancer (NSCLC). However, few analysis data were from China. Methods106 lung cancer patients who were treated with SBRT were included, their computed tomography (CT) scans were reviewed. Late injury pattern was classified by Koening’s, radiation lung fibrosis was classified by CTC 5.0, radiologists’ diagnosis for RIL was analyze. Fisher exact test was used for correlation analysis. ResultsRadiographic late injury within at least 6 months after SBRT was concluded. The majority of late RIL pattern was mass-like, not the modified conventional pattern. 36.8% patients showed acute injury. The median time for the occurrence of late injury was 8 months and 4 months for acute injury. Only per fraction dose and the occurrence of acute injury were correlated with different late injury pattern. No grade 2-5 lung fibrosis was observed. 24.5% RIL cases were misdiagnosed to tumor progression by radiologists. Most misdiagnosis occurred among mass-like pattern. We observed 13 patients with atelectasis which may be due to the irradiation of proximal bronchial tree (PBT). ConclusionsSBRT for lung cancer patients was safe, the majority of late RIL was mass-like pattern. Higher per fraction dose and the occurrence of acute injury were related with mass-like injury pattern. This injury was difficult to be distinguished from tumor progression, which leaded to misdiagnosis of 24.5% patients receiving SBRT. Moreover, the irradiated dose to PBT may be related to the atelectasis after SBRT. Legal entity responsible for the studyShanghai Chest Hospital, Shanghai Jiao Tong University. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

ACUTE FIBRINOUS AND ORGANIZING PNEUMONIA: A RARE CAUSE OF INTERSTITIAL LUNG DISEASE

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a rare cause of interstitial lung disease that is commonly misdiagnosed in patients presenting with diffuse alveolar opacities. Here we present a case of a 60-year-old previously healthy man who presented with fevers, shortness of breath and cough and was eventually diagnosed with steroid-responsive AFOP. CASE PRESENTATION: A 60-year-old otherwise healthy man presented to the hospital with shortness of breath, dry cough and recurrent fevers as high as 40C of two weeks duration. Physical exam was significant for a respiratory rate of 22, oxygen saturation on room air of 94% and bibasilar crackles. Lab work-up revealed elevated white blood cell count at 12K, erythrocyte sedimentation rate and C-reactive protein were highly elevated at >120mm and 190 mg/L, respectively. Respiratory viral panel and atypical respiratory bacterial culture were negative. Chest x-ray showed left basilar and right lower lobe opacities. After 4 days of broad-spectrum antibiotics, the patient failed to improve with paroxysmal high fevers and hypoxemia, requiring 3-5L of oxygen with nasal cannula. A high-resolution CT of the chest (Figure 1) showed worsening multi-focal parenchymal consolidation in the lower lobes and new patchy involvement in the upper lobes. Antibiotics were discontinued after bronchoscopy & bronchoalveolar lavage showed the absence of infectious organisms. Work-up for collagen vascular disease was negative. Biopsy of the lung parenchyma was done and showed prominent intra-alveolar fibrin, scattered inflammatory cells, and patchy intraluminal connective tissue consistent with AFOP. The patient was started on high dose oral prednisone of 80mg daily with a plan for a prolonged taper over 8 weeks. Over the next few days, his symptoms, oxygen requirements and chest X-ray findings all improved. The patient was discharged home with no oxygen supplementation. DISCUSSION: One of the rare histologic interstitial pneumonias, AFOP was first reported in 2002 (1). It is defined as a subgroup of idiopathic interstitial lung disease with acute lung injury characterized by intra-alveolar fibrin deposition and organization of loose connective tissue (2). Patients with AFOP tend to present with pulmonary as well as extra-pulmonary symptoms. Cough, both productive and non-productive, has been found to be the most common symptom, followed by dyspnea and fever. While AFOP can present as an idiopathic disease process, it has been found to be associated with other disease processes as well including autoimmune, infectious and connective tissue diseases.Treatment consists of systemic glucocorticoids and immunosuppression (3). CONCLUSIONS: AFOP is a rare histopathological diagnosis that requires a high degree of clinical suspicion for diagnosis. Increasing awareness of this entity might lead to earlier diagnosis and more prompt initiation of appropriate therapy. Reference #1: Beasley MB, Franks TJ, Galvin JR, et al. Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med 2002;126:1064. Reference #2: Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013;188(6):733–48. Reference #3: Bhatti S, Hakeem A, Torrealba J, et al. Severe acute fibrinous and organizing pneumonia (AFOP) causing ventilatory failure: successful treatment with mycophenolate mofetil and corticosteroids. Respir Med 2009;103:1764. DISCLOSURES: No relevant relationships by Shameek Gayen, source=Web Response No relevant relationships by Xiang Liu, source=Web Response No relevant relationships by Mahmoud Madi, source=Web Response

Acute Respiratory Distress Syndrome Definition, Causes, and Pathophysiology.

First successfully described in 1967, acute respiratory distress syndrome has since garnered much interest and debate. Extensive studies and clinical trials have been carried out in efforts to address the associated high mortality; however, it remains a significant burden on health care. Despite the heterogeneous etiologies that lead to the development of acute respiratory distress syndrome, this rapidly progressing form of respiratory failure, characterized by severe hypoxemia and nonhydrostatic pulmonary edema, has a recognizable pattern of lung injury. In this chapter, we will review the clinical manifestations, definitions, causes, and a brief overview of the pathophysiology of this complex syndrome.

The IL-33-ST2 Pathway Contributes to Ventilator-Induced Lung Injury in Septic Mice in a Tidal Volume-Dependent Manner.

Mechanical ventilation (MV) is frequently employed to manage respiratory failure in sepsis patients and is required for the surgical management of intra-abdominal sepsis. The impact of MV varies dramatically depending on tidal volume, with even moderate tidal volume (MTV) ventilation leading to ventilator-induced lung injury, whereas low tidal volume (LTV) ventilation protects against sepsis-induced acute respiratory distress syndrome. Interleukin (IL)-33 is known to contribute to lung injury in sepsis and its release can be induced by mechanical stress. To determine the relationship between the IL-33-suppression of tumorigenicity 2 (ST2) pathway and patterns of lung injury associated with MV in sepsis, mice were subjected to cecal ligation and puncture (CLP) followed 6 h later by either MTV (10 mL/kg) or LTV (6 mL/kg) ventilation for 4 h. MTV and LTV ventilation alone for 4 h had no impact on lung injury. MTV markedly exacerbated lung injury and inflammation, while LTV significantly suppressed these parameters in septic mice. Lung and plasma levels of IL-33 ST2 were significantly elevated by CLP alone at 10 h. MTV caused further and significant increases in IL-33 and sST2 levels, while LTV significantly suppressed levels induced by CLP. Deletion of IL-33 or ST2 prevented the increase in lung injury and inflammation induced by MTV in septic mice, while administration of recombinant IL-33 in the airway reversed the protection seen with LTV. Taken together, these findings implicate the IL-33-ST2 pathway in the pro-inflammatory changes induced by the mechanical ventilation that leads to lung injury in the setting of intra-abdominal sepsis in a tidal volume-dependent manner.

Lung Injuries on Computerized Tomography Due to Pellet Gun

Pellet gun used by law enforcement agencies have the potential to cause grevious or life threatening injuries as metallic projectiles fired at high speeds from pellet gun have potential to damage air containing organs like lungs which occupy a large portion of chest cavity and lie in close approximation to chest wall. Thoracic injury overall is the third most common cause of trauma following injury to the head and extremities.&#x0D; Objective. The objective of this study was to evaluate lung pellet gun injuries in patients of a conflict zone by a so called non-lethal weapon.&#x0D; Methods. The study was conducted in post graduate department of Radiodiagnosis and Imaging, Government Medical College, Srinagar Jammu and Kashmir. Our study was performed between the 6th January 2019 to the 22th May 2019. A total of 40 patients with pellet injuries were taken up for study.&#x0D; Inclusion criteria were patients with pellet gun injuries without any immediate life threatening injury like head injury; patients willing to be part of study. Radiographs of all the patients were studied. Whenever there was suspicion of severe injury, CT scan was done. We obtained thin-section axial CT scans (0.625– 1.25 mm) with multiplanar reformation with an interval of 3-5 mm.&#x0D; Results. All of the patients were males with most of patients in age group of 20 to 30 years.&#x0D; About 14 patients out of 40 had lung injuries. The most common pattern of lung injury was pneumothorax followed by pulmonary hemorrhage.&#x0D; In conclusion, a so called non-lethal pellet gun used by law enforcement agencies has the potential to cause lung injuries which can sometimes be lethal to life especially when fired from short distance.

Fatal Palbociclib -Related Interstitial Pneumonitis

Palbociclib is indicated in combination with an aromatase inhibitor for first line treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. We report a case of a 71-year-old patient with metastatic breast cancer who developed fatal diffuse parenchymal lung injury three months after the initiation of palbociclib plus letrozole. The patient presented with pulmonary embolism, which masked the progression of diffuse parenchymal lung injury. As dyspnea worsened, chest CT revealed a mixed pattern of severe interstitial and alveolar lung injury. Transbronchial lung biopsy was consistent with the subacute lung injury pattern. Treatment with high dose glucocorticoids did not result in clinical improvement and the patient succumbed to respiratory failure. It is important for clinicians to be aware that fatal interstitial pmeumonitis may occur in patients who are treated with palbociclib because early diagnosis may be vital.

Smoking-Related Lung Disease

Smoke from cigarettes and other sources may induce a variety of patterns of lung injury. While smoking related lung diseases, in general, have a better prognosis than many other diffuse lung diseases, they may be a cause of significant symptoms and, in some cases, may even require lung transplantation. On histology, the manifestations of these patterns range from reversible inflammation to irreversible emphysema or fibrosis. High-resolution chest CT plays a critical role in the diagnosis of smoking related lung diseases. It has several roles including (1) helping determine diagnosis, (2) assessing the pattern of injury that is present, (3) evaluating the extent and severity of disease, and (4) determining the response to treatment. The practicing radiologist must have a knowledge of the clinical, pathologic, and imaging features of the differnent patterns of lung injury associated with smoke inhalation.

Calpain inhibition ameliorates scald burn-induced acute lung injury in rats

BackgroundThe molecular pattern of severe burn-induced acute lung injury, characterized by cell structure damage and leukocyte infiltration, remains unknown. This study aimed to determine whether calpain, a protease involved in both processes, mediates severe burn-induced acute lung injury.MethodsRats received full-thickness scald burns covering 30% of the total body surface area, followed by instant fluid resuscitation. MDL28170 (Tocris Bioscience), an inhibitor of calpain, was given intravenously 1 h before or after the scald burn. The histological score, wet/dry weight ratio, and caspase-3 activity were examined to evaluate the degree of lung damage. Calpain activity and its source were detected by an assay kit and immunofluorescence staining. The proteolysis of membrane skeleton proteins α-fodrin and ankyrin-B, which are substrates of calpain, was measured by Western blot.ResultsTime-course studies showed that tissue damage reached a peak between 1 and 6 h post-scald burn and gradually diminished at 24 h. More importantly, calpain activity reached peak levels at 1 h and was maintained until 24 h, paralleled by lung damage to some extent. Western blot showed that the levels of the proteolyzed forms of α-fodrin and ankyrin-B correlated well with the degree of damage. MDL28170 at a dose of 3 mg/kg b. w. given 1 h before burn injury not only antagonized the increase in calpain activity but also ameliorated scald burn-induced lung injury, including the degradation of α-fodrin and ankyrin-B. Immunofluorescence images revealed calpain 1 and CD45 double-positive cells in the lung tissue of rats exposed to scald burn injury, suggesting that leukocytes were a dominant source of calpain. Furthermore, this change was blocked by MDL28170. Finally, MDL28170 given at 1 h post-scald burn injury significantly ameliorated the wet/dry weight ratio compared with burn injury alone.ConclusionsCalpain, a product of infiltrating leukocytes, is a mediator of scald burn-induced acute lung injury that involves enhancement of inflammation and proteolysis of membrane skeleton proteins. Its late effects warrant further study.

Pathology-radiology correlation of common and uncommon computed tomographic patterns of organizing pneumonia

Organizing pneumonia (OP) is a common pattern of lung injury that can be associated with a wide range of etiologies. Typical and not-so-typical imaging features of OP occur, as both common and rare lung pathologies can mimic the same imaging pattern as that of OP. This article will attempt to describe the difference between confusing terminologies that have been used in the past for OP and existence of primary versus secondary OP. The role of a multidisciplinary approach as an essential component to correctly diagnose and effectively manage challenging cases of OP will be highlighted. Additionally, we will discuss the limitation of transbronchial and importance of open lung biopsy to make the correct diagnosis. One example of an emerging diagnosis in the spectrum of OP and diffuse alveolar damage is acute fibrinous and organizing pneumonia. Ultimately, the reader should feel comfortable recognizing the many variable presentations of OP and be able to participate knowledgeably in a multidisciplinary team after reading this article. OP is a disease entity with variable radiographic and distinct histological characteristics that requires a multidisciplinary approach to correctly diagnose cryptogenic OP. Classic radiologic findings of OP occur in as low as 60% of cases. Secondary causes include infections, neoplasms, inflammatory disorders, and iatrogenic. Acute fibrinous and organizing pneumonia can appear similarly, but miliary nodules are a clue to diagnosis.

Pneumotoxicity associated with immune checkpoint inhibitor therapies

Immune checkpoint inhibitor therapies represent a new paradigm in cancer therapeutics, in which the targets are not the cancer cells, but the body's own immune system. Harnessing the immune system to better fight cancer has generated a unique spectrum of immune-related adverse events (IrAEs) that effect virtually every major organ system. Although lung involvement is less common than other forms of IrAEs, its consequences are potentially lethal. This review focuses on the evolving spectrum of lung toxicities associated with the two major classes of immune checkpoint inhibitor therapies, cytotoxic T-cell ligand-4, and programed cell death-1 (PDL-1). Lung injury was not reported in the earliest clinical trials of immune checkpoint inhibitors. More recent studies, however, have described unique radiographic and clinical toxicity profiles that differ significantly from lung injury patterns associated with conventional cytotoxic therapies. The pathophysiologic mechanisms of immune-related lung injury, its radiographic and clinical disease spectrum, associated risk factors, and optimal treatment strategies remain poorly understood. Adverse immune-mediated lung events are increasingly recognized as unique and potentially life-threatening sequelae of checkpoint inhibitor therapies. Early recognition of symptoms and radiographic abnormalities is essential to proper management and successful outcome.

Quality and Dose Optimized CT Trauma Protocol - Recommendation from a University Level-I Trauma Center.

Purpose As a supra-regional level-I trauma center, we evaluated computed tomography (CT) acquisitions of polytraumatized patients for quality and dose optimization purposes. Adapted statistical iterative reconstruction [(AS)IR] levels, tube voltage reduction as well as a split-bolus contrast agent (CA) protocol were applied. Materials and Methods 61 patients were split into 3 different groups that differed with respect to tube voltage (120 - 140 kVp) and level of applied ASIR reconstruction (ASIR 20 - 50 %). The CT protocol included a native acquisition of the head followed by a single contrast-enhanced acquisition of the whole body (64-MSCT). CA (350 mg/ml iodine) was administered as a split bolus injection of 100 ml (2 ml/s), 20 ml NaCl (1 ml/s), 60 ml (4 ml/s), 40 ml NaCl (4 ml/s) with a scan delay of 85 s to detect injuries of both the arterial system and parenchymal organs in a single acquisition. Both the quantitative (SNR/CNR) and qualitative (5-point Likert scale) image quality was evaluated in parenchymal organs that are often injured in trauma patients. Radiation exposure was assessed. Results The use of IR combined with a reduction of tube voltage resulted in good qualitative and quantitative image quality and a significant reduction in radiation exposure of more than 40 % (DLP 1087 vs. 647 mGyxcm). Image quality could be improved due to a dedicated protocol that included different levels of IR adapted to different slice thicknesses, kernels and the examined area for the evaluation of head, lung, body and bone injury patterns. In synopsis of our results, we recommend the implementation of a polytrauma protocol with a tube voltage of 120 kVp and the following IR levels: cCT 5mm: ASIR 20; cCT 0.625 mm: ASIR 40; lung 2.5 mm: ASIR 30, body 5 mm: ASIR 40; body 1.25 mm: ASIR 50; body 0.625 mm: ASIR 0. Conclusion A dedicated adaptation of the CT trauma protocol (level of reduction of tube voltage and of IR) according tothe examined body region (head, lung, body, bone) combined with a split bolus CA injection protocol allows for a high-quality CT examination and a relevant reduction of radiation exposure in the examination of polytraumatized patients Key Points · Dedicated adaption of the CT trauma protocol allows for an optimized examination.. · Different levels of iterative reconstruction, tube voltage and the CA injection protocol are crucial.. · A reduction of radiation exposure of more than 40 % with good image quality is possible.. Citation Format · Kahn J, Kaul D, Böning G et al. Quality and Dose Optimized CT Trauma Protocol - Recommendation from a University Level-I Trauma Center. Fortschr Röntgenstr 2017; 189: 844 - 854.

Changes in pulmonary function tests in breast carcinoma patients treated with locoregional post-mastectomy radiotherapy: results of a pilot study.

BackgroundThe aim of present pilot study was to evaluate the changes in pulmonary function tests (PFTs) after locoregional post-mastectomy radiotherapy (PMRT) in breast cancer patients.Materials and methodsTwenty consecutive patients with histopathologically confirmed breast carcinoma stages T1–T4, N1–N2, who were treated with modified radical mastectomy with neoadjuvant or adjuvant chemotherapy underwent PFTs, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow at 50%, and peak expiratory flow rate, maximum mid expiratory flow (MMEF25–75), maximal oxygen consumption (VO2max), and carbon monoxide diffusing capacity (DLCO) before, at 30 days, and at 90 days after locoregional PMRT. A two-tailed paired Student’s t-test was used to compare mean values among the variables between the groupsResultsA significant drop in FVC, FEV1, and DLCO was noticed at day 90 after the completion of locoregional PMRT with P-values 0.033, 0.042, and 0.031, respectively, while MMEF25–75 and VO2max were not significantly affected (P-values 0.075 and 0.062, respectively) favoring a restrictive lung injury pattern. However, no patient was found to be symptomatic.ConclusionA significant drop in reduction in PFTs occurred at day 90 after the completion of locoregional PMRT. PFTs shall be performed in all breast cancer patients receiving locoregional PMRT for early detection of radiation-induced lung toxicity as all patients in our cohort were found asymptomatic.

Treatment outcomes and patterns of radiologic appearance after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) for lung tumours.

To evaluate treatment outcomes and patterns of CT lung injury after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) in a series of inoperable lung lesions. 68 patients who were medically inoperable (69 lesions) without evidence of viable extrathoracic disease were included. Dose prescription was driven by tumour location (hilar/pericentral vs peripheral) and/or target volume. 52% of the lesions received a biological equivalent dose (BED10) ≥100 Gy. Assessment of tumour response was based on the Response Evaluation Criteria in Solid Tumours 1.1 criteria coupled with fluorine-18 fludeoxyglucose/positron emission tomography-CT. Toxicity monitoring was focused on treatment-related pulmonary adverse events according to the Common Terminology Criteria for Adverse Events v. 4.0. Acute and late events were classified as radiation pneumonitis (RP) and radiation fibrosis (RF), respectively. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate analyses of survival were performed using the Cox proportional hazards model. After a median follow-up of 12 months (range, 3-31 months), no instances of ≥Grade 4 RP was documented, and clinically severe (Grade 3) RP occurred in 5.8% of the patients. 2 (3%) patients developed a late severe (≥Grade 3) symptomatic RF. No specific pattern of CT lung injury was demonstrated, in both acute and late settings. Median overall survival (OS) and progression-free survival (PFS) for the entire population were 30.8 and 14.1 months, respectively. At multivariate analysis (MVA), BED10 ≥ 100 Gy and KPS ≥ 90 emerged as significant prognostic factors for OS (p = 0.01 and p = 0.001, respectively), and BED10 ≥ 100 Gy for PFS (p = 0.02). Our findings show that HHT adjusted for tumour location and/or target volume is an effective treatment with an acceptable toxicity profile in patients who are medically inoperable with lung tumours and is not associated with a specific pattern of lung injury. Therefore, it can represent a viable option when conventional stereotactic ablative radiotherapy facilities are not available. Advances in knowledge: The present study is among the largest series addressing the role of HHT for inoperable lung tumours. This technique is safe and effective and is not associated with a specific pattern of lung injury, at least at early and average time points.

Similar molecular subtypes of lung injury patterns in interstitial lung disease, stem cell and lung transplantation

Similar molecular subtypes of lung injury patterns in interstitial lung disease, stem cell and lung transplantation

PUB014 Nivolumab- Induced Acute Lung Injury in Non-Small Cell Lung Cancer Patients

Nivolumab (Nivo) is a promising and hopeful drug for patients with advanced lung cancer. It is one of immune checkpoint inhibitors targeting programmed cell death protein and brings about the beneficial effect for melanoma, non-small cell lung cancer and renal cell cancer. Over the next few years it is clear that immune checkpoint inhibitor therapy will play an important role in cancer therapy. In this report, we present three patterns of nivo-induced acute lung injury that have experienced in our institute. Three patterns of lung injury are as follows. Firstly, a 65-year-old male with squamous cell cancer after surgery who was administered with nivo in two weeks prior to the short breath and dyspnea. The laboratory findings showed high level of KL-6 (777 U/ml) and surfactant protein-D(1271ng/ml). On chest CT ground glass and reticular shadow were observed in the left lower lobe of the lung. Three times of pulse steroid therapy was carried out at early stage however, the patient was dead on 4 weeks after treatment of nivo. Pathological examination in the damaged lung showed the nonspecific interstitial pneumonia. Secondarly, a 69-year-old female with adenocarcinoma after surgery who was administered with nivo in two days prior to massive hemoptysis and severe respiratory dysfunction prssented. On chest CT, some massive shadows induced by acute alveolar hemorrhage at left lower lobe of lung occurred and the patient resulted in the severe respiratory failure and was dead on the same day. Lastly, A 61-year-old male with squamous cell cancer after surgery who was administered with nivo in a week without any subjective symptoms presented. On chest CT, ground glass shadow at right upper lobe of lung. The Infiltrating shadow along the bronchiovascular bundle was also observed. The pulse steroid therapy was carried out and resulted in the rapid improvement of interstitial change and inflammatory changes in the serum within a week. We have recently experienced three patterns of nivolumab-induced lung injury. As frequent use of nivo will be expected, we have to elucidate a detailed mechanism of lung injury related to this therapy as soon as possible.