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B-cell lymphoma is the most prevalent type of non-Hodgkin lymphoma, for which the standard treatment regimen includes rituximab combined with CHOP. However, some patients may develop interstitial pneumonitis (IP), which can be caused by various factors; one of the most important factors is Pneumocystis jirovecii. It is crucial to investigate the pathophysiology of IP and implement preventive measures since IP can be fatal for some people. The data were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, where patients with B-cell lymphoma received the R-CHOP/R-CDOP regimen with or without prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX). Multivariable logistic regression and propensity score matching (PSM) were used to investigate any potential association. Eight hundred thirty-one patients with B-cell lymphoma were classified into two groups: the non-prophylaxis group without TMP-SMX (n=699) and the prophylaxis group with TMP-SMX (n = 132). IP occurred in 66 patients (9.4%, all in the non-prophylaxis group), with an onset median of three cycles of chemotherapy. Multiple logistic regression analysis demonstrated that IP incidence was associated with pegylated liposome doxorubicin (OR=3.29, 95% CI 1.84–5.90, P<0.001). After utilizing a 1:1 matching algorithm for PSM, 90 patients from each group were obtained. There was a statistical difference between the two cohorts in the IP incidence (non-prophylaxis 12.2% vs prophylaxis 0.0%, P <0.001). The prophylactic use of TMP-SMX could prevent the occurrence of IP whose risk factor was pegylated liposome doxorubicin after chemotherapy for B-cell lymphoma. [ABSTRACT FROM AUTHOR]

During the first wave of the COVID�19 pandemic, a patient with anti-synthetase syndrome (ASS) was misdiagnosed as having bilateral severe acute respiratory syndrome coronavirus 2 pneumonia on admission. A comprehensive clinical evaluation would have led to the correct diagnosis earlier, as he had some data consistent with ASS on both physical examination and laboratory tests that were initially overlooked. In addition, a malignant lesion in the colon was found on screening for underlying malignancy. In this context, ASS has been considered a low-risk subgroup for cancer among idiopathic inflammatory myopathies. However, this should be interpreted cautiously and should not lead to neglect of adequate cancer screening adjusted for age, sex and other potential risk factors. [ABSTRACT FROM AUTHOR]

The second-generation anticonvulsant lamotrigine is widely used in the psychiatric field as a mood stabilizer or antidepressant augmentation therapy. Although particularly older anticonvulsants are known for their potential to cause hypersensitivity syndromes, newer antiepileptic drugs do hold a certain risk as well. Presenting a case of a 32-year-old male inpatient of African ethnicity suffering from a primary severe depressive episode in the course of a recurrent major depressive disorder, we report the occurrence of a rapid-onset drug- induced pneumonitis. Herewith, the interstitial pneumonitis occurred after the initiation of 25 mg lamotrigine as an augmentation therapy. Except for the clear temporal correlation between the administration of lamotrigine and the onset of pneumonitis, we did not reveal any further potentially causal diagnostic hints. Importantly, no relevant genetic variations of metabolizing enzymes or drug interactions resulting in lamotrigine overdosage as a potential cause of toxicity were identified. Our experience with a potentially life-threatening adverse drug reaction shortly after the initiation of the largely well-tolerated lamotrigine suggests a potential side effect under the second-generation anticonvulsant although similar adverse events are deemed to be very rare. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of aqueous leaf extract of Kalanchoe pinnataon Bifenthrin-induced injury in the lungs of adult Wistar rats. The 30 adult Wistar rats weighing between 250g and 280g that were used in this research were divided into 5 groups of 6 rats per group. The haematological outcome showed that Bifenthrin caused some derangements in haematological parameters especially lymphocytes and basophils, haemoglobin and red blood cells with associated reticulocytosis. Histologically, marked bronchiolar dilation, marked alveolar dilatation and severe vascular ulceration were observed in the rats exposed to bifenthrin only. Kalanc hoepinnata showed no negative effects on the histology of the lungs as the alveoli and the bronchial artery of the rats treated with Kalanchoe pinnata extract were found to be histologically normal when compared with the control. In conclusion, Kalanchoe pinnata has ameliorative effects against bifenthrin-induced injury in the lung of Wistar rats and its effect is inversely proportional to dosage. It is more potent at low doses. [ABSTRACT FROM AUTHOR]

Anti-cancer treatments for lung cancer patients with interstitial lung disease (ILD) are challenging. The treatment options for ILD are often limited because of concerns that treatments can cause acute exacerbation (AE) of ILD. This study aimed to analyze the outcomes of carbon-ion radiotherapy (CIRT) for stage I non-small cell lung cancer (NSCLC) with ILD, using a multi-institutional registry. Patients with ILD who received CIRT for stage I NSCLC in CIRT institutions in Japan were enrolled. The indication for CIRT was determined by an institutional multidisciplinary tumor board, and CIRT was performed in accordance with institutional protocols. Thirty patients were eligible. The median follow-up duration was 30.3 months (range, 2.5–58 months), and the total dose ranged from 50 Gy (relative biological effectiveness [RBE]) to 69.6 Gy (RBE), and five different patterns of fractionation were used. The beam delivery method was passive beam in 19 patients and scanning beam in 11 patients. The 3-year overall survival (OS), cause-specific survival, disease-free survival (DFS) and local control (LC) rates were 48.2%, 62.2%, 41.2% and 88.1%, respectively. Grade > 2 radiation pneumonitis occurred in one patient (3.3%). In conclusion, CIRT is a safe treatment modality for stage I NSCLC with concomitant ILD. CIRT is a safe and feasible treatment option for early lung cancer in ILD patients. [ABSTRACT FROM AUTHOR]

Abstract Background Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized. Methods A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation. Results Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05–8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60–184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78–1.04; P = 0.160) and 1.49 (95% CI, 0.95–2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34–50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89–7.92; P = 0.12) and 0.66 (95% CI, 0.03–4.55; P = 0.71), respectively, using ICI monotherapy as reference. Conclusions Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP.

The second-generation anticonvulsant lamotrigine is widely used in the psychiatric field as a mood stabilizer or antidepressant augmentation therapy. Although particularly older anticonvulsants are known for their potential to cause hypersensitivity syndromes, newer antiepileptic drugs do hold a certain risk as well. Presenting a case of a 32-year-old male inpatient of African ethnicity suffering from a primary severe depressive episode in the course of a recurrent major depressive disorder, we report the occurrence of a rapid-onset drug-induced pneumonitis. Herewith, the interstitial pneumonitis occurred after the initiation of 25 mg lamotrigine as an augmentation therapy. Except for the clear temporal correlation between the administration of lamotrigine and the onset of pneumonitis, we did not reveal any further potentially causal diagnostic hints. Importantly, no relevant genetic variations of metabolizing enzymes or drug interactions resulting in lamotrigine overdosage as a potential cause of toxicity were identified. Our experience with a potentially life-threatening adverse drug reaction shortly after the initiation of the largely well-tolerated lamotrigine suggests a potential side effect under the second-generation anticonvulsant although similar adverse events are deemed to be very rare.

The aim of this study was to investigate the effects of aqueous leaf extract of Kalanchoe pinnataon Bifenthrin-induced injury in the lungs of adult Wistar rats. The 30 adult Wistar rats weighing between 250g and 280g that were used in this research were divided into 5 groups of 6 rats per group. The haematological outcome showed that Bifenthrin caused some derangements in haematological parameters especially lymphocytes and basophils, haemoglobin and red blood cells with associated reticulocytosis. Histologically, marked bronchiolar dilation, marked alveolar dilatation and severe vascular ulceration were observed in the rats exposed to bifenthrin only. Kalanc hoepinnata showed no negative effects on the histology of the lungs as the alveoli and the bronchial artery of the rats treated with Kalanchoe pinnata extract were found to be histologically normal when compared with the control. In conclusion, Kalanchoe pinnata has ameliorative effects against bifenthrin-induced injury in the lung of Wistar rats and its effect is inversely proportional to dosage. It is more potent at low doses.

Rituximab is a chimeric monoclonal antibody against CD20+ lymphocytes used to treat non-Hodgkin lymphoma, hematological and autoimmune diseases rheumatoid arthritis, systemic lupus erythematosus, thrombocytopenic purpura, hemolytic anemia, multiple sclerosis. The safety of the drug is critical to the choice of treatment. Rituximab-associated interstitial lung disease is rare. Objective. To describe a case of interstitial pneumonitis induced by rituximab in monotherapy at the end of maintenance therapy. Materials and methods. We describe a case of a 37-year-old patient with stage IIB non-Hodgkin lymphoma involving palatine tonsils and cervical and submandibular lymph nodes on both sides. Histologically, this tumor was a diffuse large B-cell lymphoma. Results. A patient received six R-CHOP courses of chemotherapy and immunotherapy for stage IIB diffuse large B-cell lymphoma. After the therapy, a complete clinical and metabolic response was achieved. Rituximab maintenance therapy was administered at a dose of 375 mg/m2 every 2 months for 2 years. At this treatment stage, combined positron emission tomography and 18F-fluorodeoxyglucose computed tomography (PET/CT with 18F-FDG) was performed at 45 months intervals. No radiological signs of pulmonary diseases were detected. Seven weeks after the last dose of rituximab (24 months), another PET/CT with 18F-FDG showed radiological changes that were considered to be interstitial pneumonitis, with no respiratory signs of the disease. No signs of tumor progression were found. Conclusion. Rituximab may contribute to late pulmonary toxicity presented as interstitial pneumonitis in non-Hodgkin lymphoma patients at a young age after maintenance therapy for 24 months. PET/CT with 18F-FDG is the primary method of diagnosing pulmonary toxicity.

Background: Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized. Methods: A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation. Results: Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05–8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60–184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78–1.04; P = 0.160) and 1.49 (95% CI, 0.95–2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34–50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89–7.92; P = 0.12) and 0.66 (95% CI, 0.03–4.55; P = 0.71), respectively, using ICI monotherapy as reference. Conclusions: Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP. [ABSTRACT FROM AUTHOR]

Introduction: Androgen deprivation therapy remains the essential treatment for disseminated prostate cancer. Interstitial pneumonitis following this therapy has been documented for just a few cases. However, reported cases frequently describe the onset of symptoms after recent administration (days or a few weeks) of both GnRH analogues and androgen antagonists, which makes the precise individual impact of each treatment difficult to estimate. Case report: This report presents a case of a 94-year-old patient with interstitial pneumonitis whose onset started three months after the first dose of leuprorelin and bicalutamide for a metastatic prostate cancer. Management and outcome: Once other possible diagnosis were ruled out, empiric corticosteroid treatment was initiated within 48 h of the admission. A spectacular clinical and radiological improvement was observed after 3 doses of steroids, enabling the patient to recover his basal respiratory situation. We considered that the most probable cause was toxic interstitial pneumonitis induced by leuprorelin. Discussion: To our knowledge, it describes the longest interval between last administration of antiandrogen therapy and the development of pneumonitis. This fact may support a direct relation with leuprorelin, whose serum levels remain high for months because of its long-acting depot formulation. [ABSTRACT FROM AUTHOR]

Abstract Background Non-intubated video-assisted thoracic surgery is a therapeutic option for intractable secondary spontaneous pneumothorax in patients who are poor candidates for surgery with endotracheal intubation under general anesthesia. However, intraoperative respiratory management in this surgery is often challenging because of hypoxia caused by surgical pneumothorax. Case presentation A 75-year-old man with idiopathic pulmonary fibrosis who had been on home oxygen therapy underwent non-intubated uniportal video-assisted thoracic surgery for intractable spontaneous pneumothorax. During the operation, oxygen was administered using a high-flow nasal cannula at a high flow rate. An air-locking port for single-incision surgery was used to minimize the inflow of air into the pleural cavity. The intrapleural air was continuously suctioned through the chest tube. The air-leak point was easily identified and closed using ligation. Oxygenation was satisfactory throughout the operation. Conclusions Non-intubated uniportal video-assisted thoracic surgery for secondary spontaneous pneumothorax with an air-locking port, continuous pleural suction, and high-flow nasal cannula may achieve satisfactory intraoperative oxygenation in patients with respiratory dysfunction. The intrapleural space can be feasible for surgical manipulation without surgical pneumothorax in non-intubated video-assisted thoracic surgery even when supplied with oxygen at a high flow rate using a high-flow nasal cannula.

Ga-68 labeled prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) is increasingly recognized as the best imaging modality for disease staging and detection of recurrent prostate cancer. Despite its name, PSMA expression has been reported in the neovasculature of several nonprostatic benign and malignant pathologies. Docetaxel, a taxane antineoplastic agent, is the mainstay of treatment in castration-resistant prostate cancer and high-volume hormone-sensitive prostate cancer. Although the occurrence of docetaxel-related interstitial lung disease is rare, it may lead to respiratory failure if treatment is delayed. We present a case of metastatic castration-resistant prostate cancer, wherein docetaxel-induced interstitial pneumonitis was detected on Ga-68 PSMA PET/CT after docetaxel administration. [ABSTRACT FROM AUTHOR]

Sri Lanka is one of few countries which has performed post mortem examinations in deaths due to SARS CoV-2 virus (COVID-19) infection. At the office of the Judicial Medical Officer of National Institute of Infectious Diseases (NIID)/Infectious Disease Hospital (IDH) we have performed over sixty (60) post mortem examinations of deceased persons who were confirmed positive for COVID-19 by Real Time - Polymerase Chain reaction (RT-PCR) test performed before or after death. They included a majority of deaths due to natural causes and few deaths due to unnatural causes such as accidents, suicides and homicides. The first autopsy was performed on 04th of May 2020. We have observed acute lymphocytic interstitial pneumonitis (ALIP) as a potentially fatal complication in COVID-19 infection at the initial stages of lung involvement. This phenomenon of early onset ALIP has not been reported in the literature of COVID-19 lung pathophysiology to date. This is a narrative of our histological findings. Our attempt is to highlight the importance early onset ALIP as a pathological entity in COVID-19 lung involvement, which will enhance the clinicians to better understand the pathophysiology of this new illness and modify their treatment strategies.

Methotrexate (MTX) is the commonly preferred drug in the treatment of various chronic inflammatory conditions. An uncommon, life-threatening, and fatal event associated with methotrexate use is methotrexate-induced pneumonitis (M-pneu). M-pneu does not correlate with the dosage, duration, or method of administration. We present a case of M-pneu in a diagnosed rheumatoid arthritis patient after six years of initiation of MTX. Prompt recognition, withdrawal, and supportive therapy have a positive outcome. If untreated, M-pneu has a proven fatality of 17–30% in published cases.

Introduction: Trastuzumab emtansine (TDM-1) is an antibody–drug conjugate effective in human epidermal growth factor receptor-2 - expressing advanced breast cancer. Pulmonary complications of TDM-1 are rarely reported. TDM-1-associated interstitial lung disease is referred to as pneumonitis. Case report: A 47-year-old female patient who underwent modified radical mastectomy and axillary lymph node dissection operations due to a palpable mass in the right breast and axillary region. The patient who had received multiple chemotherapy was last receiving TDM-1 treatment. Fatigue, dyspnea, and tachypnea were detected for the first time on 20 days after the 6th treatment. Menagement and outcome: In our case, we first considered metastasis, pneumonia and fungal infection based on radiological findings, but the lack of response to the treatments and the results of the investigations suggested drug-induced pneumonia and steroid treatment was started. Our case had a complete radiological recovery and complete response to sterod therapy. In such cases, it is important to first exclude infections and metastasis. In cases of drug-induced pneumonia, the first treatment option is systemic corticosteroids and generally responded well. Discussion: Unlike other cases of interstitial pneumonia, lung imaging of our case was resembling a metastasis, pneumonia and fungal infection. With increasing use of TDM-1, we will have more experience in both efficacy and complications of TDM-1. Although TDM-1 is a well-tolerated drug, clinicians should be aware of rare pulmonary complications and prepared to respond appropriately. [ABSTRACT FROM AUTHOR]

Interstitial lung diseases (ILD) or diffuse parenchymal lung diseases (DPLD) comprise a large number of disorders. Disease definition and classification allow advanced and personalized judgements on clinical disease, risks for genetic or environmental transmissions, and precision medicine treatments. Registers collect specific rare entities and use ontologies for a precise description of complex phenotypes. Here we present a brief history of ILD classification systems from adult and pediatric pneumology. We center on an etiologic classification, with four main categories: lung-only (native parenchymal) disorders, systemic disease-related disorders, exposure-related disorders, and vascular disorders. Splitting diseases into molecularly defined entities is key for precision medicine and the identification of novel entities. Lumping diseases targeted by similar diagnostic or therapeutic principles is key for clinical practice and register work, as our experience with the European children's ILD register (chILD-EU) demonstrates. The etiologic classification favored combines pediatric and adult lung diseases in a single system and considers genomics and other -omics as central steps towards the solution of "idiopathic" lung diseases. Future tasks focus on a systems' medicine approach integrating all data and bringing precision medicine closer to the patients. [ABSTRACT FROM AUTHOR]

Abstract Background The diagnosis of check-point inhibitor-related pneumonitis (CIP) relies on radiological and clinical patterns which are not specific and can mimic other conditions (cancer progression, infectious diseases or interstitial pneumonitis). Cell pattern analysis of bronchoalveolar lavage (BAL) is well-known to support the diagnosis of interstitial lung disease; nevertheless, this analysis is somewhat performed and not required by immune-toxicity management guidelines for CIP. Methods We performed BAL analysis in 5 metastatic melanoma (MM) patients who developed CIP among 112 patients treated with checkpoint inhibitors. We also correlated the BAL features with the computed tomography (CT) scan patterns and with various peripheral blood parameters to better define the profile of this patient population. Results BAL flow cytometer and cytopathology analyses showed typical and homogeneous features with increased lymphoid population, prevalent CD8 + T cells and inversion of the CD4/CD8 ratio. Moreover, the extent of activated CD3 + HLA-DR + T cells was related to the grading of adverse events. Blood leucocytosis, hypoxemia, normal values for procalcitonin and lactate dehydrogenase were also found together with a cryptogenic organizing pneumonia-like radiologic pattern. In all our patients, CIP was associated with partial or complete response. Conclusions Identification of a specific BAL cellular pattern allows clinicians to place this investigation in the appropriate position of CIP diagnosis and management to avoid misdiagnosis or considering this condition as progressive disease and delaying proper treatment.

BackgroundInterstitial lung diseases (ILDs) are disorders of the lung parenchyma. The pathogenesis, clinical manifestations, and prognosis of ILDs vary depending on the underlying disease. The onset of most ILDs is insidious, but they may also present subacutely or require hospitalization for management. ILDs that may present subacutely include acute interstitial pneumonia, connective tissue disease-associated ILDs, cryptogenic organizing pneumonia, acute eosinophilic pneumonia, drug-induced ILDs, and acute exacerbation of idiopathic pulmonary fibrosis. Prognosis and response to therapy depend on the type of underlying ILD being managed.DiscussionThis opinion piece discusses approaches to differentiating ILDs in the hospitalized patient, emphasizing the role of bronchoscopy and surgical lung biopsy. We then consider pharmacologic treatments and the use of mechanical ventilation in hospitalized patients with ILD. Finally, lung transplantation and palliative care as treatment modalities are considered. The diagnosis of ILD in hospitalized patients requires input from multiple disciplines. The prognosis of ILDs presenting acutely vary depending on the underlying ILD. Patients with advanced ILD or acute exacerbation of idiopathic pulmonary fibrosis have poor outcomes. The mainstay treatment in these patients is supportive care, and mechanical ventilation should only be used in these patients as a bridge to lung transplantation.

It is accepted that 2-3% of interstitial lung diseases (ILD) are due to drugs, and that 70% of drug-induced lung diseases are due to ILD. We present here the case of a 51-year-old female patient who had been taking aripiprazole for bipolar disorder for 3 years and had been undergoing asthma treatment for 2 years. ILD was considered based on the patient's clinic, a restrictive pattern in the pulmonary function test (PFT), a decreased carbon monoxide diffusion test, laboratory results, radiological findings and biopsy. The possible etiologies of infection, aspiration, heart failure, pet feeding status and exposure to hazardous respiratory substances were excluded. The suspected drug was discontinued and oral corticosteroid treatment was started. Lung toxicity can develop with drug treatments, and so drug history should be questioned in detail and discontinued immediately in case of any doubt. ILD is rare, and if the drug is not suspected and continued, the disease may become chronic and progress to respiratory failure. We present this case to increase awareness of the disease. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor-modified T cells (CAR-T) targeting CD19 has produced a high durable response in refractory or relapsed diffuse large B-cell lymphoma. Besides well-known cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome during CAR-T cell therapy, there were several rarely encountered fatal complications. Case Report: A 63-year-old male patient with refractory EBV-positive diffuse large B-cell lymphoma, developed interstitial pneumonitis with prolonged hypoxemia at 16 weeks after CD19 CAR-T cell therapy. There was no evidence of CRS and any infections. The patient recovered after intravenous immunoglobulin without tocilizumab or glucocorticoid administration. Now he is still in remission without interstitial pneumonitis 3 years after CAR-T cell therapy. Conclusion: This is the first report of immunotherapy-associated interstitial pneumonitis after CAR-T cell therapy. Our finding suggested the importance of careful follow-up and proper treatments for immunotherapy-associated pneumonitis in the CAR-T cell therapy schedule. [ABSTRACT FROM AUTHOR]

Abstract Background Intravesical administration of Bacillus Calmette–Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. Case presentation A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. Conclusions We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.

BackgroundChimeric antigen receptor-modified T cells (CAR-T) targeting CD19 has produced a high durable response in refractory or relapsed diffuse large B-cell lymphoma. Besides well-known cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome during CAR-T cell therapy, there were several rarely encountered fatal complications.Case ReportA 63-year-old male patient with refractory EBV-positive diffuse large B-cell lymphoma, developed interstitial pneumonitis with prolonged hypoxemia at 16 weeks after CD19 CAR-T cell therapy. There was no evidence of CRS and any infections. The patient recovered after intravenous immunoglobulin without tocilizumab or glucocorticoid administration. Now he is still in remission without interstitial pneumonitis 3 years after CAR-T cell therapy.ConclusionThis is the first report of immunotherapy-associated interstitial pneumonitis after CAR-T cell therapy. Our finding suggested the importance of careful follow-up and proper treatments for immunotherapy-associated pneumonitis in the CAR-T cell therapy schedule.

Background: Non-intubated video-assisted thoracic surgery is a therapeutic option for intractable secondary spontaneous pneumothorax in patients who are poor candidates for surgery with endotracheal intubation under general anesthesia. However, intraoperative respiratory management in this surgery is often challenging because of hypoxia caused by surgical pneumothorax. Case presentation: A 75-year-old man with idiopathic pulmonary fibrosis who had been on home oxygen therapy underwent non-intubated uniportal video-assisted thoracic surgery for intractable spontaneous pneumothorax. During the operation, oxygen was administered using a high-flow nasal cannula at a high flow rate. An air-locking port for single-incision surgery was used to minimize the inflow of air into the pleural cavity. The intrapleural air was continuously suctioned through the chest tube. The air-leak point was easily identified and closed using ligation. Oxygenation was satisfactory throughout the operation. Conclusions: Non-intubated uniportal video-assisted thoracic surgery for secondary spontaneous pneumothorax with an air-locking port, continuous pleural suction, and high-flow nasal cannula may achieve satisfactory intraoperative oxygenation in patients with respiratory dysfunction. The intrapleural space can be feasible for surgical manipulation without surgical pneumothorax in non-intubated video-assisted thoracic surgery even when supplied with oxygen at a high flow rate using a high-flow nasal cannula. [ABSTRACT FROM AUTHOR]

Pulmonary involvement is common in children with scrub typhus. Our paper outlines the clinical characteristics of pulmonary involvement and analyses the predictors of its severity. All scrub typhus serology-positive (optical density >0.5) children with pulmonary symptoms were included. Of 506 serology-positive scrub typhus cases, 256 (50.5%) had pulmonary symptoms, of whom 50 (9.8%) were severe. These severe cases were compared with non-severe cases. Interstitial pneumonitis was the commonest chest radiographic finding. Logistic regression analysis identified 'fever clearance time' >48 h, facial puffiness, maculopapular rash and anaemia to be significantly associated with severe pulmonary involvement. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is the commonly preferred drug in the treatment of various chronic inflammatory conditions. An uncommon, life-threatening, and fatal event associated with methotrexate use is methotrexate-induced pneumonitis (M-pneu). M-pneu does not correlate with the dosage, duration, or method of administration. We present a case of M-pneu in a diagnosed rheumatoid arthritis patient after six years of initiation of MTX. Prompt recognition, withdrawal, and supportive therapy have a positive outcome. If untreated, M-pneu has a proven fatality of 17–30% in published cases. [ABSTRACT FROM AUTHOR]

Abstract Firstly, glucocorticoids such as prednisolone can attenuate the effect of anti–PD‐1 antibody nivolumab. Secondly, malignant melanoma cells survived latently and unnoticeably in places other than those of previous metastatic lesions. Thirdly, effector T cells activated by nivolumab sustained their memory to attack malignant melanoma cells for several months.

Abstract Background Interstitial pneumonitis is a rare reaction in a previously irradiated area of pulmonary or thoracic lesion after treatment with anticancer drugs such as taxanes. Case presentation A 66-year-old man presented with a fever and dyspnea after treatment with cabazitaxel for castration-resistant prostate cancer. He was treated with an intravenous broad-spectrum antimicrobial agent, however he complained of dyspnea and had a pulse oximetric saturation of 80% while breathing room air. The patients had been treated for bone metastases with 37.5 Gy to the thoracic spine (Th 7) as a local radiotherapy. Radiological images showed pulmonary interstitial opacities in the irradiated field of the both lungs. The steroid pulse therapy was started. The patient’s dyspnea disappeared and the interstitial opacities had also improved. Conclusions This report is a case of interstitial pneumonitis in a castration-resistant prostate cancer patient receiving cabazitaxel after thoracic radiation therapy.

Abstract Low‐dose imatinib with monitoring of drug concentrations in blood may successfully control Philadelphia chromosome‐positive mixed phenotype acute leukemia (Ph+MPAL), particularly in elderly patients with comorbidities.

Low‐dose imatinib with monitoring of drug concentrations in blood may successfully control Philadelphia chromosome‐positive mixed phenotype acute leukemia (Ph+MPAL), particularly in elderly patients with comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: The increasing application of immune checkpoint inhibitors (ICIs) will cause more checkpoint inhibitor‐related pneumonitis (CIP), which is a common cause of ICI‐related death. The clinical management of CIP needs further optimization. Methods: Patients who were managed at Peking Union Medical College Hospital (PUMCH) between February 2017 and December 2019 with a diagnosis of CIP were retrospectively analyzed. Clinical data including clinical manifestations, radiologic data, laboratory and bronchoscopy results, treatments, and outcomes were collected and analyzed. The Mann–Whitney test was used to compare patients with and without co‐infections. Results: In total, 48 CIP cases in 42 patients were analyzed. The median time from the first dose of ICI to the onset of CIP was 1.9 months (range: 0.1–13.7). Grade 3–4 (G3–4) accounted for 30 cases (71.4%). The most common symptoms were cough (88.1%) and dyspnea (78.6%). The median starting dose of equivalent prednisone (EP) was 55 mg (range: 30–200) for all patients. The median total duration of glucocorticosteroids (GCS) treatment was 42.5 days (range: 15−89). Three patients (7.14%) died because of infection. A higher starting dose and longer duration of GCS (≥30 mg/day; p = 0.001) were associated with opportunistic infection. Chest computed tomography (CT) showed diverse and asymmetrical lesions. Twelve patients were re‐challenged, and six patients developed recurrent CIP. Conclusions: The clinical and imaging manifestations of CIP are various, and differential diagnosis of exclusion is essential. GCS at 1–2 mg/kg is feasible to treat CIP, but the duration of GCS ≥30 mg/day should be used with caution, given the high risk of acquired infections. Re‐challenges of ICI are feasible, but the recurrence of CIP needs to be closely monitored. [ABSTRACT FROM AUTHOR]

Eosinophilia in not an uncommon findings in the intensive care unit (ICU); however, DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome, which is characterized by a hypersensitivity reaction to drugs and manifests as eosinophilia, systemic involvement and maculopapular erythematous rash 2-6 weeks after exposure to the offending drug, is an exceptional occurrence. We present the first case described in the literature of DRESS syndrome with pulmonary involvement in the form of interstitial pneumonitis and persistent adult respiratory distress syndrome (ARDS) secondary to proton pump inhibitors (PPI). The patient made a good recovery after withdrawal of the offending drug and long-term treatment with systemic corticosteroids. We also present a systematic review of all cases of DRESS with pulmonary involvement in the form of interstitial pneumonitis and cases of PPI-induced DRESS published to date; none of these describe pulmonary involvement., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Background: The diagnosis of check-point inhibitor-related pneumonitis (CIP) relies on radiological and clinical patterns which are not specific and can mimic other conditions (cancer progression, infectious diseases or interstitial pneumonitis). Cell pattern analysis of bronchoalveolar lavage (BAL) is well-known to support the diagnosis of interstitial lung disease; nevertheless, this analysis is somewhat performed and not required by immune-toxicity management guidelines for CIP.Methods: We performed BAL analysis in 5 metastatic melanoma (MM) patients who developed CIP among 112 patients treated with checkpoint inhibitors. We also correlated the BAL features with the computed tomography (CT) scan patterns and with various peripheral blood parameters to better define the profile of this patient population.Results: BAL flow cytometer and cytopathology analyses showed typical and homogeneous features with increased lymphoid population, prevalent CD8 + T cells and inversion of the CD4/CD8 ratio. Moreover, the extent of activated CD3 + HLA-DR + T cells was related to the grading of adverse events. Blood leucocytosis, hypoxemia, normal values for procalcitonin and lactate dehydrogenase were also found together with a cryptogenic organizing pneumonia-like radiologic pattern. In all our patients, CIP was associated with partial or complete response.Conclusions: Identification of a specific BAL cellular pattern allows clinicians to place this investigation in the appropriate position of CIP diagnosis and management to avoid misdiagnosis or considering this condition as progressive disease and delaying proper treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is defined as a severe, progressive lymphoproliferative disorder associated with active EBV infection persisting longer than 6 months and developing in patients without recognised immunodeficiency. Rarely, interstitial pneumonitis (IP) occurs as a serious complication in CAEBV patients. The standard therapeutic regimen for IP in CAEBV has not yet been defined. Although interferon alpha (IFN-alpha) is known to suppress viral DNA replication by affecting its basal promoter activation process, it is rarely used in CAEBV patients. Case presentation A 22-year-old Caucasian woman, diagnosed with CAEBV 1.5 years earlier, was admitted to the Immunology Clinic due to a 4-week history of productive cough, fever and general weakness. Cultures of blood, urine and sputum were negative, but EBV DNA copies were found in the sputum, whole blood, isolated peripheral blood lymphocytes as well as in the blood plasma. Cytokine assessment in peripheral blood revealed the lack of IFN-alpha synthesis. Disseminated maculate infiltrative areas in both lungs were observed on a computed tomography (CT) chest scan. The patient was not qualified for the allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to the risk of immunosuppression-related complications of infectious IP. Inhaled (1.5 million units 3 times a day) and subcutaneous (6 million units 3 times a week) IFN-alpha was implemented. To the best of our knowledge, this was the first documented use of inhaled IFN-alpha in a patient with CAEBV and concomitant IP. Patient’s status has improved, and she was eventually qualified to allo-HSCT with reduced conditioning. Currently, the patient feels well, no EBV was detected and further regression of pulmonary changes was documented. Conclusions CAEBV should be considered in patients who present with interstitial lung infiltration and involvement of other organs. Although more promising results have been obtained with allo-HSCT, inhaled IFN-alpha may also be a therapeutic option in patients with CAEBV and a concomitant IP.

Abstract Background Primary central nervous system lymphoma(PCNSL) is a rare kind of non-Hodgkin lymphoma. Rituximab combined with high-dose methotrexate, cytarabine and dexamethasone (R-MAD regimen) were reported effective for PCNSL patients. Rituximab can cause several side effects, including fever, chills and rigors. Case presentation In this case report, we demonstrate rituximab-induced interstitial pneumonitis in a PCNSL patient who has been treated with R-MAD regimen. The patient recovered after treatment and she remains complete remission after following consolidation chemotherapy. Conclusions Here is no report of potential fatal complications of Rituximab like interstitial pneumonitis nowadays in PCNSL patients. As Rituximab is widely used, physicians should raise their awareness of this rare complication and detect RTX-ILD in early stage.

Bevacizumab is a vascular endothelial growth factor–directed humanized monoclonal antibody used to treat many types of cancer and some eye diseases. Due to inhibition of angiogenesis, many adverse reactions such as bowel necrosis, nasal septal perforation, and renal thrombotic microangiopathy have been described. However, its association with interstitial pneumonitis is scarcely reported in the literature. We report a case of a 79-year-old woman with metastatic colon cancer who presented with cough and dyspnea on exertion the day after initiation of bevacizumab. She was found to have bilateral airspace opacities on imaging. Infectious and cardiogenic etiologies of dyspnea were ruled out. Due to the temporal relationship with the initiation of chemotherapy, she was suspected to have developed bevacizumab-induced interstitial pneumonitis. She improved rapidly with high-dose steroids. Follow-up imaging showed resolution of infiltrates. This is the first reported case in the literature that directly links bevacizumab to interstitial pneumonitis. [ABSTRACT FROM AUTHOR]

Background: In clinical practice, chemotherapy-induced interstitial pneumonitis (CIIP) is rare, but it has a high mortality. It has been reported that pegylated liposomal doxorubicin (PLD) may induce interstitial pneumonitis in some cases. However, the relationship between PLD and CIIP in breast cancer is still unknown. This study aims to investigate the incidence of PLD-induced interstitial pneumonitis in breast cancer patients.Methods: All cases of breast cancer with chemotherapy are collected in our hospital from January 2016 to October 2018, and 354 eligible patients were included in analysis. Patients were divided into two groups according to different chemotherapy regimens received: epirubicin plus cyclophosphamide with or without docetaxel (EC/EC-T group) and PLD plus cyclophosphamide with or without docetaxel (DC/DC-T group). Patients' general information and clinical characteristics, as well as the incidence of interstitial pneumonitis were compared between the two groups.Results: The symptomatic interstitial pneumonitis occurred in 12 patients who received DC/DC-T treatment with an incidence of 12.25% (12/98), while no interstitial pneumonitis occurred in EC/EC-T group (p < 0.001). Of the 12 patients, 4 patients developed interstitial pneumonitis after 3 cycles of chemotherapy,7 patients after 4 cycles and 1 patient after 5 cycles. The mean interval between the beginning of chemotherapy and the onset of CIIP was 3.75 cycles.Conclusion: Clinicians should pay attention to CIIP in breast cancer patients who receive more than three cycles of chemotherapy regimens containing pegylated liposomal doxorubicin plus cyclophosphamide with or without docetaxel. [ABSTRACT FROM AUTHOR]

Surfactant protein C (SP-C) disorder is a major component of hereditary interstitial lung disease (HILD) among Japanese. The correlation between clinical outcomes and the phenotype/genotype of SP-C disorder has not been evaluated comprehensively. The current study aimed to evaluate the phenotype/genotype correlated with poor outcomes in patients with SP-C disorder. Sequencing analysis of SFTPC in 291 candidates with HILD was performed. The phenotype and genotype correlated with poor outcomes were examined. The log-rank test was used to compare the probability of good outcomes between two patient groups. Twenty patients were diagnosed with SP-C disorder. Of nine patients with neonatal-onset disease, four and five presented with pulmonary alveolar proteinosis (PAP) and interstitial pneumonitis (IP), respectively. The remaining 11 patients with late-onset disease had IP. In total, four and 16 patients had PAP and IP phenotypes, respectively. Four of nine patients with neonatal-onset disease died, and one survived after lung transplant. Further, 1 of 11 patients with late-onset disease died. Four patients with neonatal-onset PAP had a significantly lower probability of good outcomes than the remaining patients. Two patients with neonatal-onset PAP had the p.Leu45Arg variant, one died and the another survived after lung transplant. Of eight patients with variants in the BRICHOS domain, one with frame shift variant located in exon 4, one with variant located at the splicing acceptor site of exon 4, and one with variant located at the splicing donor site of exon 4 died. Neonatal-onset PAP was a phenotype predicting poor outcomes in patients with SP-C disorder. The p.Leu45Arg variant and splicing disorder of exon 4 might be genotypes predicting poor outcomes in patients with SP-C disorder. • This is the first report showing that neonatal-onset pulmonary alveolar proteinosis is a phenotype correlated with poor outcomes in children with SP-C disorder. • The pathogenic variations in the SFTPC gene did not accumulate in the BRICHOS domain in children. • SFTPC p.Leu45Arg might be associated with severe respiratory symptoms. • Splicing disorder of SFTPC exon 4 might be the genotype predicting poor outcomes. [ABSTRACT FROM AUTHOR]

Altmış yedi yaşında kadın hasta bir aydır halsizlik, nefes darlığı ve öksürük yakınması ile başvurdu. Hasta 2007 yılında sağ memede invaziv duktal karsinom nedeniyle cerrahi ve radyoterapi tedavisi gördüğünü ve dört ay önce de akciğerde multipl metastatik lezyonların saptanması üzerine everolimus tedavisine (10 mg/gün) başlanmış. Tedaviden sonra hastada everolimusa bağlı intersitisyel akciğer hastalığı saptandı.. Everolimus nispeten güvenli bir oral anti-kanser ajanıdır ancak interstisyel akciğer hastalığı ciddi bir yan etki olarak bildirilmiştir. Bu olgu Everolimusa bağlı ciddi akciğer toksisitesini göstermek için sunulmuştur.

Firstly, glucocorticoids such as prednisolone can attenuate the effect of anti–PD‐1 antibody nivolumab. Secondly, malignant melanoma cells survived latently and unnoticeably in places other than those of previous metastatic lesions. Thirdly, effector T cells activated by nivolumab sustained their memory to attack malignant melanoma cells for several months. [ABSTRACT FROM AUTHOR]

Conversion surgery is an attractive strategy to improve the outcomes for locally advanced unresectable (UR-LA) pancreatic ductal adenocarcinoma (PDAC). The present case report, presents a case of successful conversion surgery following the treatment of a patient with UR-LA PDAC, suffering from interstitial pneumonitis (IP), using a combination of gemcitabine and nab-paclitaxel (GnP). A 67-year-old woman presented at the hospital with a high level of carbohydrate antigen 19-9 (CA19-9; 1,713 U/ml). Radiological examination revealed a pancreatic tumor in contact with the superior mesenteric artery, with invasion extending to the most proximal draining jejunal branch into the superior mesenteric vein. The patient was diagnosed with UR-LA PDAC. Following 6 courses of GnP therapy, the tumor size markedly decreased from 50 to 18 mm, and the level of CA19-9 also decreased from 1,713 to 60.1 U/ml. Due to the progression of IP, the patient was administered steroid medication along with a restart of tacrolimus for the treatment of dermatomyositis and IP. After recovery from her lung condition, an additional 3 courses of GnP therapy were administered, and then pancreatoduodenectomy was performed. The patient was still alive 14 months post-surgery with no recurrence. Between July 2009 and September 2017, conversion surgery was performed for 18 cases of UR-LA PDAC treated with gemcitabine plus S-1 (GS) therapy, and 11 cases with GnP therapy. The percentage of median CA19-9 and median tumor volume reductions were 73.7 and 51.6%, respectively, following GS therapy, and 86.7 and 68.8%, respectively, following GnP therapy. Tumor reduction following GnP therapy was significantly higher than that after GS therapy (P=0.02). GnP therapy is a suitable regimen to shrink the tumor mass in patients with UR-LA PDAC. Careful management of systemic conditions is required to treat patients with PDAC and IP when using GnP therapy. Conversion surgery should be considered for recognizing radiological responses (tumor shrinkage adjacent to major arteries) and reductions in CA19-9 levels. [ABSTRACT FROM AUTHOR]

This is a case report of pulmonary damage in the form of intestinal pneumonitis with severe respiratory failure during administration of acetaminophen (paracetamol). In addition, significant increase of ALT and AST levels without clinical signs of liver damage was observed in this patient. After glucocorticoids administration regression of radiological abnormal findings in the lungs along with normalization of liver enzymes values were registered. The rarity of interstitial pneumonitis induced by acetaminophen (paracetamol), especially in combination with liver damage, is emphasized. The presented patient history is the first case report of drug-induced hepatopulmonary syndrome during acetaminophen (paracetamol) administration.

Methotrexate (MTX) is an antimetabolite used as a disease-modifying agent for various rheumatological conditions. We report two patients who were treated with daily low-dose MTX and developed acute interstitial pneumonitis requiring hospital admission. MTX-induced pneumonitis is a rare life-threatening side effect, high index of clinical suspicion is required, treatment is mainly withdrawal of MTX, supportive therapy, and adjunctive steroids, outcome is good if condition is recognized early, and appropriate treatment is given.