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The etiology and pathologic findings of bovine respiratory disease (BRD) in adult dairy cows (n = 35) from a commercial dairy herd in Southern Brazil were investigated. Pulmonary samples were examined for histopathologic patterns and specific features within these patterns, while immunohistochemical (IHC) assays were designed to detect the intralesional antigens of viral infectious disease agents and Mycoplasma bovis. Pneumonia was diagnosed in 91.4% (32/35) of these cases; neither pneumonia nor any of the infectious disease pathogens evaluated occurred in three cows. The presence of multiple respiratory pathogens in 75% (24/32) of these cases indicated the complex origin of pneumonia in cattle. Interstitial pneumonia, necrosuppurative bronchopneumonia and suppurative bronchopneumonia were the principal patterns of pulmonary disease identified by histopathology. The most frequent pathogens identified by IHC were bovine viral diarrhea virus (BVDV; n = 18), M. bovis (n = 16) and bovine alphaherpesvirus type 1 (BoHV‐1; n = 14), followed by bovine respiratory syncytial virus (BRSV; n = 11) and bovine parainfluenza virus type 3 (BPIV‐3; n = 5). Obliterative bronchiolitis and peribronchial lymphocytic cuffings were the characteristic histopathologic features associated with M. bovis. Necrohemorrhagic bronchitis with bronchial angiogenesis was associated with BoHV‐1. Necrotizing bronchitis and bronchiolitis were associated with BVDV, BoHV‐1 and BRSV. Ballooning degeneration of the bronchial and bronchiolar epithelia was associated with BRSV and BoHV‐1. This is the first report from Brazil that correlated the histopathologic findings of BRD with the associated infectious disease agents by immunohistochemistry. M. bovis was frequently detected in the tissues of cows with fatal pulmonary disease during this study and may be a possible primary disease pathogen associated with the development of BRD in dairy cows. Additionally, the histopathologic features identified within patterns of pulmonary disease during this investigation may be an efficient diagnostic tool to associate histopathologic findings with specific agents of BRD in dairy cows. [ABSTRACT FROM AUTHOR]

In the setting of the coronavirus disease 2019 (COVID-19) pandemic, only few data regarding lung pathology induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is available, especially without medical intervention interfering with the natural evolution of the disease. We present here the first case of forensic autopsy of a COVID-19 fatality occurring in a young woman, in the community. Diagnosis was made at necropsy and lung histology showed diffuse alveolar damage, edema, and interstitial pneumonia with a geographically heterogeneous pattern, mostly affecting the central part of the lungs. This death related to COVID-19 pathology highlights the heterogeneity and severity of central lung lesions after natural evolution of the disease. [ABSTRACT FROM AUTHOR]

Bedside chest ultrasonography, when integrated with clinical data, is an accurate tool for improving the diagnostic process of many respiratory diseases. This study aims to evaluate the feasibility of a chest ultrasonographic screening program in nursing homes for detecting coronavirus disease-19 (COVID-19)–related pneumonia and improving the appropriateness of hospital referral of residents. Pragmatic, descriptive, feasibility study from April 2 to April 9, 2020. A total of 83 older residents (age 85 ± 8) presenting mild to moderate respiratory symptoms and not previously tested for COVID-19, residing in 5 nursing homes in Northern Italy. Chest ultrasonography was performed at the bedside by a team of hospital specialists with certified expertise in thoracic ultrasonography, following a systematic approach exploring 4 different areas for each hemithorax, from the anterior and posterior side. Presence of ultrasonographic signs of interstitial pneumonia, including comet-tail artifacts (B-lines) with focal or diffuse distribution, subpleural consolidations, and pleural line indentation, was detected. The specialist team integrated ultrasonography data with clinical and anamnestic information, and gave personalized therapeutic advice for each patient, including hospital referral when needed. The most frequent reasons for ultrasonographic evaluation were fever (63% of participants) and mild dyspnea (40%). Fifty-six patients (67%) had abnormal ultrasonographic findings. The most common patterns were presence of multiple subpleural consolidations (32 patients) and diffuse B-lines (24 patients), with bilateral involvement. A diagnosis of suspect COVID-19 pneumonia was made in 44 patients, and 6 of them required hospitalization. Twelve patients had ultrasonographic patterns suggesting other respiratory diseases, and 2 patients with normal ultrasonographic findings were diagnosed with COPD exacerbation. In nursing home residents, screening of COVID-19 pneumonia with bedside chest ultrasonography is feasible and may represent a valid diagnostic aid for an early detection of COVID-19 outbreaks and adequate patient management. [ABSTRACT FROM AUTHOR]

A 22-y-old American Quarter Horse gelding was presented with a history of chronic progressive respiratory problems and a diffuse pulmonary nodular pattern in thoracic radiographs. The horse was euthanized, and 4 formalin-fixed samples of lung were submitted for histopathology. There were multifocal areas of marked thickening of alveolar septa as a result of proliferation of myofibroblasts embedded in fibromyxoid matrix (interpreted as "Masson bodies"), focal areas of fibrosis, and numerous papillary projections of connective tissue into bronchioles. A diagnosis of organizing pneumonia was reached. No etiology was found for this lesion. It is important to consider causes of chronic interstitial pneumonia with fibrosis in horses other than equid herpesvirus 5, such as complicated viral or bacterial pneumonia or chronic toxicoses. [ABSTRACT FROM AUTHOR]

Since December 2019, a novel Coronavirus (SARS-CoV-2) was confirmed as the etiologic agent of a worldwide outbreak of a pneumonia that can result in severe respiratory failure. This clinical entity seems to be associated with a marked hypercoagulable state that causes both arterial and venous thromboembolic complications. Therefore, an adequate anti-thrombotic prophylaxis is recommended in hospitalized COVID-19 patients. Although rapidly worsening respiratory symptoms in a patient with SARS-CoV-2 respiratory infection may correlate with worsening pneumonia itself, it may also mask a pulmonary embolism. We report the case of a 50-year-old man affected by SARS-CoV-2 pneumonia, who developed acute pulmonary embolism. [ABSTRACT FROM AUTHOR]

Background: Approximately 10% of patients with non-small cell lung cancer (NSCLC) are complicated with comorbid interstitial pneumonia (IP) with a poor prognosis. The pharmacotherapy for advanced lung cancer occasionally induces fatal acute exacerbation of pre-existing IP. Due to the lack of prospective studies, there is an urgent need to establish a safe and effective pharmacotherapy, especially for second-line or later settings. Atezolizumab, an anti-programmed cell death-ligand 1 antibody, is thought to be the safest candidate for second-line therapy among various immune checkpoint inhibitors. Moreover, compared with patients without IP, the patients with comorbid IP may have higher tumor mutation burden (TMB) or microsatellite instability (MSI), which are partly associated with a more favorable response to immune checkpoint inhibitors. Methods: The Thoracic Oncology Research Group 1936/AMBITIOUS study is an ongoing, multicenter, single-arm, phase II trial to assess the safety and efficacy of atezolizumab for pretreated advanced/recurrent patients with NSCLC complicated with idiopathic, chronic fibrotic IP with a forced vital capacity of >70%. The patients will receive atezolizumab (1200 mg, day 1) every 3 weeks until the discontinuation criteria are met. The primary end point of this study is the 1-year survival rate, and a sample size of 38 patients is set. As a translational research, we will perform the analysis of TMB, somatic mutations, and MSI for nucleic acids extracted from archival tumor samples. Discussion: Since there is no standard second-line or later therapy of advanced NSCLC with IP, the results of this study are expected to have a major impact on clinical practice. Trial registration: Japan Registry of Clinical Trials, jRCTs031190084, registered 26 August 2019 - retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190084 [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 infection has as a clinical manifestation the disease known as COVID-191. Although knowledge of the nature of the disease is dynamic, with dozens of scientific articles being published every day about new features of COVID-19, the typical presentation is that of interstitial pneumonia2. Despite the large amount of information that has been developed in recent weeks, it has been estimated that this disease can have up to 72% underdiagnosis3, which requires clinical tools that are simple, easily accessible, and increase the detection of cases in a feasible way and that yield information with prognostic value. Given this need, some proposals have emerged to be able to diagnose, monitor and respond to the treatment of patients with COVID-19, such as pulmonary ultrasound (USP). It is worth mentioning that the USP has proven to be an efficient and easily reproducible technique for diagnosing heart failure and pleuro-pulmonary pathologies, especially in critically ill patients4-7. Evidence of the usefulness of USP in COVID-19 is still scarce, although preliminary, it seems to be a sensitive technique whose findings have a high gold standard. In this brief review we will emphasize its technical aspects, the advantages and disadvantages, and finally a proposal for the approach in this type of patient. [ABSTRACT FROM AUTHOR]

Objective Interstitial pneumonia is common and has high short-term mortality in patients with PM and DM despite glucocorticoid (GC) treatment. Retrospective studies suggested that the early use of immunosuppressive drugs with GCs might improve its short-term mortality. Methods A multicentre, single-arm, 52-week-long clinical trial was performed to test whether the initial combination treatment with tacrolimus (0.075 mg/kg/day, adjusted for the target whole-blood trough levels between 5 and 10 ng/ml) and GCs (0.6–1.0 mg/kg/day of prednisolone followed by a slow taper) improves short-term mortality of PM/DM-interstitial pneumonia patients. The primary outcome was overall survival. We originally intended to compare, by using propensity-score matching, the outcome data of clinical trial patients with that of historical control patients who were initially treated with GCs alone. Results The 52-week survival rate with the combination treatment (N = 26) was 88.0% (95% CI, 67.3, 96.0). Safety profiles of the combination treatment were consistent with those known for tacrolimus and high-dose GCs individually. Serious adverse events occurred in 11 patients (44.0%), which included four opportunistic infections. Only 16 patients, including only 1 deceased patient, were registered as historical controls, which precluded meaningful comparative analysis against the clinical trial patients. Conclusion Our study provided findings which suggest that initial treatment with tacrolimus and GCs may improve short-term mortality of PM/DM-interstitial pneumonia patients with manageable safety profiles. This was the first prospective clinical investigation conducted according to the Good Clinical Practice Guideline of the International Conference on Harmonization for the treatment of this potentially life-threatening disease. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov , NCT00504348. [ABSTRACT FROM AUTHOR]

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• Right ventricular (RV) longitudinal function deteriorated with increasing severity of idiopathic interstitial pneumonias (IIPs). • RV function was independently associated with mortality in moderate-stage IIPs. • In severe-stage IIPs, not RV function but brain natriuretic peptide level was associated with mortality. Few studies have examined the relationship between echocardiographic indices of right ventricular (RV) function and the severity of pulmonary disease, or their prognostic impact. We evaluated the RV function in patients with interstitial pneumonia and its prognostic impact at each stage of disease severity. A total of 176 patients with idiopathic interstitial pneumonias (IIPs) were retrospectively enrolled and we evaluated RV function by transthoracic echocardiography. The severity of IIPs was graded according to the Goh score. The primary outcome was all-cause death. There were 55 patients in mild group (31%), 66 in moderate group (38%), and 55 in severe group (31%). Regarding RV function, RV free wall longitudinal strain and tricuspid annular plane systolic excursion (TAPSE) deteriorated with increasing severity of IIPs, but fractional area change (FAC) decreased significantly only in severe group. There were 64 all-cause deaths during the follow-up period (median 908 days). In moderate group, TAPSE [hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.74–0.97, p = 0.017], FAC (HR: 0.89, 95% CI: 0.83–0.96, p = 0.001), and mean pulmonary artery pressure (PAP)/cardiac output (HR: 1.50, 95% CI: 1.08–2.09, p = 0.015) were independent predictors of all-cause death, even after adjusting for age and log brain natriuretic peptide (BNP). On the other hand, not RV function or PAP but male sex and BNP level were associated with mortality in severe group. Among patients with IIPs, RV longitudinal function deteriorated with increasing severity of IIPs. Echocardiographic indices of RV function were independently associated with mortality in moderate-stage IIPs. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an autoimmune disease that can cause fibrosis in vital organs, often resulting in damage to the skin, blood vessels, gastrointestinal system, lungs, heart, and/or kidneys. Patients with SSc are also likely to develop microstomia, which can render dental treatment difficult and painful, thereby necessitating advanced anesthetic management. This is a case report of a 61-year-old woman with a history of SSc with microstomia, interstitial pneumonia, and gastroesophageal reflux disease in whom intravenous moderate sedation was performed using a combination of dexmedetomidine and ketamine for dental extractions. Both anesthetic agents are known to have analgesic effects while minimizing respiratory depression. Consequently, the increased discomfort caused by opening the patient's mouth and stretching the buccal mucosa was sufficiently managed, permitting an increase in maximum interincisal opening and completion of treatment without complications. Patients with SSc present with serious comorbidities that can negatively impact anesthetic management, so the implementation of an anesthetic plan that takes such risks into account is required. Furthermore, emergency airway management is likely to be difficult in patients with microstomia. For intravenous moderate sedation, combined use of dexmedetomidine and ketamine, which have analgesic effects while minimizing respiratory depression, may be particularly effective in patients with SSc and microstomia. [ABSTRACT FROM AUTHOR]

Background: Acute exacerbation (AE) of interstitial lung disease (ILD) is a fatal adverse event in the treatment of lung cancer patients with ILD. The value of pre-treatment radiological findings obtained by high-resolution computed tomography for the detection of anticancer treatment-related AE of ILD has not been established. Methods: Two medical record-based retrospective studies were performed. The chemotherapy cohort included 105 lung cancer patients with ILD who received chemotherapy at Tokyo Medical and Dental University between October 2008 and December 2017. The immune checkpoint inhibitor (ICI) cohort included 48 advanced non-small cell lung cancer patients with ILD treated with ICIs at nine institutions between January 2016 and September 2018. Variables were compared between AE-positive and -negative groups. Candidate variables were analyzed by multivariate logistic regression. A P value < 0.05 was considered statistically significant. Results: Anticancer treatment-related AE of ILD occurred in 12 patients (11.4%) in the chemotherapy cohort and seven patients (14.5%) in the ICI cohort. In the multivariate logistic regression analysis, ground-glass attenuation (GGA) score was the only factor significantly associated with the development of AE of ILD in both cohorts (P = 0.037 and 0.01 in the chemotherapy and ICI cohorts, respectively). Conclusion: Evaluation of GGA may help predict anticancer treatment-related AE of ILD. [ABSTRACT FROM AUTHOR]

The association between gut microbiota and the lung immune system has been attracting increasing interest. Here, we report a case of pancreatic cancer in which the dipeptidyl peptidase‐4 inhibitor vildagliptin induced unusual manifestations of interstitial pneumonia, possibly under the influence of Lactobacillus paraplantarum probiotic supplementation. Chest computed tomography and positron emission tomography showed multiple ground‐glass nodules (GGNs) mimicking metastatic lung cancer. Transbronchial biopsy specimens showed mild fibrosis and infiltration of lymphocytes consisting of more CD4+ than CD8+ cells. The CD4+ cells did not include FOXP3+ regulatory T cells. Bronchoalveolar lavage confirmed lymphocytosis with a markedly increased CD4+/CD8+ ratio of 7.4. The nodules disappeared shortly after vildagliptin and probiotics were withheld. If unusual interstitial pneumonia is observed in some cancer patients, physicians should pay careful attention to their medication history, including probiotic supplements. [ABSTRACT FROM AUTHOR]

Capillary leak syndrome (CLS) is a rare but fatal disease, which has been reported following the infusions of interleukin-2, tumor necrosis factor, granulocyte-colony stimulating factor, certain monoclonal antibodies, and gemcitabine, suggesting that drugs can also cause CLS. In this study, seven Wilm's tumor cases with CLS had been presented, which was suggested to be caused following administration of vincristine (VCR). From January 1st, 2014 to December 31st, 2016, medical records from Wilm's tumor patients were reviewed to identify those diagnosed with CLS. Moreover, the following data were extracted for each patient, including age, gender, histological subtyping, tumor stage, risk group, biomarkers, chemotherapy regimen and dosage, surgery details, clinical manifestation of CLS, treatment regimen of CLS, and patient outcomes. From January 1st, 2014 to December 31st, 2016, a total of seven patients with Wilms tumor were identified with a diagnosis of VCR-associated CLS. Typically, for these seven cases in our study, the predominant features of CLS included interstitial pneumonia and pulmonary edema. Moreover, steroid therapy was demonstrated as the most effective therapy in our study. The clinical features of VCR-induced CLS are distinct, and pediatric oncologists should be aware of CLS that manifests as interstitial pneumonia and pulmonary edema during the VCR treatment for patients with Wilm's tumor. [ABSTRACT FROM AUTHOR]

• Pulmonary affection is the most important disease form caused by Small Ruminant Lentiviruses in sheep. • The infection is mostly transmitted by aerosols and clinical signs can appear in animals one year old, onwards. • Third generation ELISAs are the most suitable definitive diagnostic tools. • Lung gross lesions are the most useful tools for a presumptive diagnosis. • Control of the infection is easier to achieve than eradication. Pulmonary affection is by far the most severe and widespread disease form caused by Small Ruminant Lentiviruses (SRLV) in sheep. The infection implies direct contact between animals and the most important infection route is by the respiratory tract. Disease is insidious and might be seen in one-year-old animals onwards. Non-productive dyspnea is the most common clinical sign and interstitial pneumonia with increased lung size and volume are the pathologic landmarks. Early detection of infected animals is a key step for the diagnosis and it is best achieved by third generation ELISAs that include a multistrain design to detect divergent genotypes. Differential diagnosis must be established with ovine pulmonary adenocarcinoma, the visceral form of ovine caseous lymphadenitis, ovine respiratory complex, gangrenous pneumonia and bacterial and parasitic (Dyctiocaulus filaria , Oestrus ovis) infections. Control is achieved by combining serological and management measures and is based on total or selective culling of infected animals and replacement with uninfected lambs. Serological segregation and replacement with the offspring of seronegative ewes is also a suitable option for control. Selection of resistant sheep might be a future option. Pulmonary affection by SRLV in sheep must be taken into account in the face of a chronic, non-productive dyspnea. [ABSTRACT FROM AUTHOR]

The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not effective in halting disease progression. Connective tissue growth factor (CTGF), also known as cellular communication factor 2 (CCN2), is a member of the CCN family of proteins that regulates cell signaling through cell surface receptors such as integrins, the activity of cytokines/growth factors, and the turnover of extracellular matrix (ECM) proteins. Accumulating evidence indicates that CTGF plays a crucial role in promoting lung fibrosis through multiple processes, including inducing transdifferentiation of fibroblasts to myofibroblasts, epithelial-mesenchymal transition (EMT), and cooperating with other fibrotic mediators such as TGF-β. Increased expression of CTGF has been observed in fibrotic lungs and inhibiting CTGF signaling has been shown to suppress lung fibrosis in several animal models. Thus, the CTGF signaling pathway is emerging as a potential therapeutic target in IPF and other pulmonary fibrotic conditions. This review provides a comprehensive overview of the current evidence on the pathogenic role of CTGF in pulmonary fibrosis and discusses the current therapeutic agents targeting CTGF using a systematic review approach. [ABSTRACT FROM AUTHOR]

We present a case of a 45-year-old woman diagnosed with interstitial pneumonia (IP) during a comprehensive breast cancer evaluation. Although the patient showed no obvious clinical symptoms of polymyositis or dermatomyositis, the presence of anti-glycyl-transfer ribonucleic acid synthetase antibodies confirmed anti-synthetase syndrome. The patient began methylprednisolone for treatment of the IP. She then received preoperative chemotherapy with epirubicin and cyclophosphamide before undergoing a mastectomy. A significant improvement was seen in the patient's IP during treatment. This case emphasizes the potential advantages of personalized immunosuppressive therapy for patients who are simultaneously diagnosed with anti-synthetase syndrome and cancer. [ABSTRACT FROM AUTHOR]

A 74-year-old man was referred to our hospital with an abnormal chest shadow. Computed tomography (CT) revealed a mass in the left upper lobe and interstitial pneumonia (IP). The patient underwent CT-guided needle biopsy and was diagnosed as lung adenocarcinoma with cT2aN1M1a Stage IVA (PUL). The patient was administered 6 cycles of CBDCA + nab-paclitaxel as first-line, 3 cycles of atezolizumab as second-line, and 8 cycles of S-1 as third-line treatment but finally showed tumor progression. Because comprehensive genome profiling test revealed KRAS G12C mutation, sotorasib was initiated as fourth-line treatment and showed tumor regression without exacerbation of pre-existing IP. [ABSTRACT FROM AUTHOR]

Background: Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may cause an acute multiorgan syndrome (coronavirus disease 2019 (COVID-19)), data are emerging on mid- and long-term sequelae of COVID-19 pneumonia. Since no study has hitherto investigated the role of both cardiac and pulmonary ultrasound techniques in detecting such sequelae, this study aimed at evaluating these simple diagnostic tools to appraise the cardiopulmonary involvement after COVID-19 pneumonia. Methods: Twenty-nine patients fully recovered from COVID-19 pneumonia were considered at our centre. On admission, all patients underwent 12-lead electrocardiogram (ECG) and transthoracic echocardiography (TTE) evaluation. Compression ultrasound (CUS) and lung ultrasound (LUS) were also performed. Finally, in each patient, pathological findings detected on LUS were correlated with the pulmonary involvement occurring after COVID-19 pneumonia, as assessed on thoracic computed tomography (CT). Results: Out of 29 patients (mean age 70 ± 10 years; males 69%), prior cardiovascular and pulmonary comorbidities were recorded in 22 (76%). Twenty-seven patients (93%) were in sinus rhythm and two (7%) in atrial fibrillation. Persistence of ECG abnormalities from the acute phase was common, and nonspecific repolarisation abnormalities (93%) reflected the high prevalence of pericardial involvement on TTE (86%). Likewise, pleural abnormalities were frequently observed (66%). TTE signs of left and right ventricular dysfunction were reported in two patients, and values of systolic pulmonary artery pressure were abnormal in 16 (55%, despite the absence of prior comorbidities in 44% of them). Regarding LUS evaluation, most patients displayed abnormal values of diaphragmatic thickness and excursion (93%), which correlated well with the high prevalence (76%) of pathological findings on CT scan. CUS ruled out deep vein thrombosis in all patients. Conclusions: Data on cardiopulmonary involvement after COVID-19 pneumonia are scarce. In our study, simple diagnostic tools (TTE and LUS) proved clinically useful for the detection of cardiopulmonary complications after COVID-19 pneumonia.

Interstitial pneumonia is a life-threatening clinical manifestation of cytomegalovirus infection in recipients of hematopoietic cell transplantation (HCT). The mouse model of experimental HCT and infection with murine cytomegalovirus revealed that reconstitution of virus-specific CD8+ T cells is critical for resolving productive lung infection. CD8+ T-cell infiltrates persisted in the lungs after the establishment of latent infection. A subset defined by the phenotype KLRG1+CD62L− expanded over time, a phenomenon known as memory inflation (MI). Here we studied the localization of these inflationary T effector-memory cells (iTEM) by comparing their frequencies in the intravascular and transmigration compartments, the IVC and TMC, respectively, with their frequency in the extravascular compartment (EVC), the alveolar epithelium. Frequencies of viral epitope-specific iTEM were comparable in the IVC and TMC but were reduced in the EVC, corresponding to an increase in KLRG1−CD62L− conventional T effector-memory cells (cTEM) and a decrease in functional IFNγ+CD8+ T cells. As maintained expression of KLRG1 requires stimulation by antigen, we conclude that iTEM lose KLRG1 and convert to cTEM after transmigration into the EVC because pneumocytes are not latently infected and, therefore, do not express antigens. Accordingly, antigen re-expression upon airway challenge infection recruited virus-specific CD8+ T cells to TMC and EVC.

Abstract Background Eribulin is typically used to treat patients with advanced breast cancer, and anti-cancer agents often cause the development of interstitial pneumonia in Japanese patients with advanced cancer. However, few case reports have addressed eribulin-induced interstitial pneumonia. Herein, we report a rare case of interstitial pneumonia—specifically, organized pneumonia—during treatment with eribulin in a patient with advanced breast cancer. Case presentation A 52-year-old Japanese woman was diagnosed as having advanced breast cancer 3 years before the admission described in the present report. She had received eribulin as third-line chemotherapy. Five days after her second treatment with eribulin, she was admitted to our hospital with dyspnea and dry cough. Upon admission, a chest computed tomography scan showed consolidation, with air bronchograms along the bronchovascular bundle of both lower lobes. The patient’s serum levels of sialylated carbohydrate antigen Krebs von den Lungen-6 were high, as were her surfactant protein-D levels. There was no evidence of heart failure, renal failure, or infection. Based on the clinical cause, as well as on the findings of organized pneumonia, the patient was diagnosed as having interstitial pneumonia and treated with corticosteroids. After the initiation of steroid treatment, her respiratory condition and chest radiological findings improved. Conclusions This case reveals an association between eribulin treatment and interstitial pneumonia. To our knowledge, this is the first case report to describe eribulin-induced organized pneumonia. Clinicians should be aware that interstitial pneumonia can develop during treatment with anti-cancer agents.

Abstract Background Regulatory T cells (Tregs) are crucial in maintaining immune tolerance and immune homeostasis, but their role in idiopathic pulmonary fibrosis (IPF) is unclear. This study was designed to explore the role of Tregs in IPF. Methods Percentages of Tregs and their subpopulations in peripheral blood (PB) and bronchoalveolar lavage (BAL) samples were determined by flow cytometry in 29 patients with IPF, 19 patients with primary Sjögren’s syndrome-related interstitial pneumonia (pSS-IP), and 23 healthy controls (HCs). Results In peripheral blood, no difference was found in CD4+CD25+Foxp3+ Treg percentages among patients with IPF, pSS-IP, or HCs. However, activated Treg (aTreg) fractions among CD4+ T cells increased significantly in IPF compared with pSS-IP or HCs. Being consistent with the result from the PB, aTreg fractions among CD4+ T cells in IPF also increased significantly compared with pSS-IP or HCs, accompanied by increased fraction III compared with HCs in BAL. IPF patients had lower levels of resting Tregs (rTregs) from the thymus than did HCs, whereas aTreg levels originating from the thymus did not significantly differ from HCs. Both rTregs and aTregs proliferated in IPF, with aTregs being more proliferative than rTregs. Both rTregs and aTregs significantly inhibited proliferation of CD4+ T lymphocytes in vitro. The percentage of aTregs was correlated negatively with predicted diffusing capacity values for carbon monoxide and positively with GAP index in IPF. Conclusions Our study showed the imbalance between subpopulations of Tregs in IPF. Increased aTregs proportion in the peripheral blood correlated inversely with disease severity.

Abstract Background The FOLFOX regimen, i.e., folinic acid (FOL), fluorouracil (F) and oxaliplatin (OX), is a drug cocktail that is used to treat gastric and colorectal cancers. Despite the concomitant improvements in response rate, duration of response and patient survival, reports of serious toxic pulmonary side effects have progressively emerged. Case presentation We describe a patient who was treated with FOLFOX as an adjuvant to a rectosigmoidal resection of a rectosigmoidal carcinoma and who developed respiratory insufficiency requiring mechanical ventilation. Computed tomography (CT) imaging and open lung biopsy findings were compatible with interstitial pneumonia (IP). She received multimodal combination treatment (acetylcysteine, corticosteroids, immune globulins and cyclophosphamide) and survived. We performed a systematic literature search and reviewed all 45 reported cases of FOLFOX-related lung toxicity and/or pulmonary fibrosis for their clinical characteristics and their outcomes related to therapy. Conclusions We found that for the 45 cases with available data, the median age was 70 years, and the male–female ratio was 3.5: 1. In the patients exhibiting only mild respiratory symptoms, discontinuation of the culprit drug (oxaliplatin) resulted in a 100% regression of the symptoms. However the prognosis of the respiratory insufficient patient proved to be grim: death occurred in 76.9% of the cases despite conventional treatment with corticosteroids. We therefore urge oncologists and critical care specialists not to limit their interventions to the discontinuation of chemotherapy, artificial ventilation, corticosteroids and glutathione replenishment and to consider the gradual introduction of additional immune-modulating agents whenever life-threatening respiratory symptoms in oxaliplatin-treated patients do not subside; all the more so considering the fact that our analysis showed that every patient who survived intubation and mechanical ventilation experienced a full clinical recovery.

Abstract Background Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition without an established pharmaceutical treatment. Most patients are treated with high-dose corticosteroids and broad-spectrum antibiotics. Azithromycin is a macrolide with immunomodulatory activity and may be beneficial for treatment of acute lung injury. The objective of this study was to determine the effect of azithromycin on survival of patients with idiopathic AE of IPF. Methods We evaluated 85 consecutive patients hospitalized in our department for idiopathic AE of IPF from April 2005 to August 2016. The initial 47 patients were treated with a fluoroquinolone-based regimen (control group), and the following 38 consecutive patients were treated with azithromycin (500 mg/day) for 5 days. Idiopathic AE of IPF was defined using the criteria established by the 2016 International Working Group. Results Mortality in patients treated with azithromycin was significantly lower than in those treated with fluoroquinolones (azithromycin, 26% vs. control, 70%; p

Oral direct-acting antivirals (DAAs) are the main therapy for hepatitis C virus (HCV)-associated liver disease in Japan. Daclatasvir/asunaprevir is the first agent and sofosbuvir/ledipasvir is the secondary agent for HCV genotype 1b. More recently, ombitasvir/paritaprevir/ritonavir is also recommended as a potent therapy for HCV genotype 1b. Among the adverse events associated with these oral DAAs, interstitial pneumonia is one of the most severe ones. Regarding treatment with daclatasvir plus asunaprevir or sofosbuvir plus ledipasvir, a few cases have already been reported in a postmarketing surveillance. Recently, we have encountered a HCV-associated genotype 1b cirrhosis patient who developed interstitial pneumonia during treatment with ombitasvir/paritaprevir/ritonavir and who recovered after drug discontinuation without corticosteroid therapy. Interstitial pneumonia was confirmed by chest x-ray and chest computed tomography. The serum KL-6 level was elevated to 1,180 U/mL. The total duration of the drug administration was 7 weeks, and she achieved SVR24. This is the first detailed report in the literature on the development of interstitial pneumonia during treatment with ombitasvir/paritaprevir/ritonavir. When dry cough appeared in the treatment with DAAs, chest computed tomography and the evaluation of serum KL-6 level were recommended.

Abstract Background Early identification of infants at higher risk of developing bronchopulmonary dysplasia (BPD) may enable a targeted approach to reduce BPD. We aimed to evaluate the hypothesis that the interstitial pneumonia pattern on the day 7 chest radiograph predicts BPD or death before 36 weeks postmenstrual age (PMA). Methods A retrospective cohort study was performed on 336 preterm infants (birth weight

Abstract Background Goodpasture’s syndrome is a rare disease that is characterized by rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. Case presentation A 71-year-old Japanese man who had chronic interstitial pneumonia was diagnosed as having Goodpasture’s syndrome. Both anti-glomerular basement membrane antibody and myeloperoxidase anti-neutrophil cytoplasmic antibody were increased. Despite intensive treatments, including mechanical ventilation, he died from respiratory failure. Pathological findings at autopsy showed rapidly progressive glomerulonephritis in his kidneys, diffuse alveolar hemorrhage, hyaline membranes, and fibroblastic foci in his lungs. The cause of death was diagnosed as respiratory failure as a result of diffuse alveolar damage induced by a combination of diffuse alveolar hemorrhage and exacerbation of interstitial pneumonia. Conclusions We report a case of Goodpasture’s syndrome complicated with pre-existing chronic interstitial pneumonia and positive myeloperoxidase anti-neutrophil cytoplasmic antibody. We reviewed six similar cases reported in the literature and concluded that Goodpasture’s syndrome with pre-existing interstitial pneumonia and myeloperoxidase anti-neutrophil cytoplasmic antibody is related to a poor prognosis.

The objective of this study is to summarize the pharmacological effects and the mechanisms of action of Xiao Chai Hu Tang (XCHT, Minor Bupleurum Decoction) on liver diseases, so as to give relevant researchers a valuable insight and benefit patients with hepatopathy. PubMed was used to search for and collect scientific publications related to XCHT and liver diseases from 1986 to 2016. The available scientific results or evidence were read, classified, and analyzed. XCHT showed clinical efficacy in patients with hepatic diseases including hepatitis, hepatic fibrosis, and hepatoma. The mechanisms involved the production of cytokines, the regulation of immune function, the suppression of lipid peroxidation, etc., XCHT might work on the metabolism of some medications such as tolbutamide by the regulation of gastric emptying and intragastric pH. XCHT exhibited a very low toxicity profile, such as interstitial pneumonia due to duration of medication, patients' age, and drug combination. XCHT has been a eutherapeutic supplemental remedy for liver diseases. However, many mechanisms of action and effects of XCHT on new types of liver diseases still remain unclear, so more and more animal experiments and human clinical trials are needed to obtain enough proofs for the clinical use of XCHT in new types of hepatosis such as nonalcoholic fatty liver disease and autoimmune liver disease.

A 72-year-old woman was admitted to our hospital and was diagnosed with interstitial pneumonia (IP) associated with amyopathic dermatomyositis (ADM). The patient experienced three acute IP exacerbations in the 7 years that followed, which were each treated and resolved with steroid pulse therapy. The patient was closely examined for respiratory failure with right heart catheterization (RHC), which demonstrated that she had a mean pulmonary artery pressure (mPAP) of 34 mmHg. The patient was thus diagnosed as having pulmonary hypertension (PH) associated with anti-synthetase syndrome (ASS) and was started on bosentan therapy, which led to improvements in mPAP as well as in subjective symptoms over time. Indeed, she had had no acute exacerbations with serum markers of IP remaining low over 6 years following initiation of bosentan therapy, suggesting that bosentan may have a role in controlling IP. In addition, she was confirmed to be anti-ARS antibody-positive after 5 years of bosentan therapy, when anti-aminoacyl tRNA synthetase (anti-ARS) antibody testing became available.

Objective: This study is dedicated to revealing the potential mechanism of Qin Run Hua Jie (QRHJ) decoction in Interstitial pneumonia (IP) treatment., Methods: The TCMSP database predicted the chemical components and targets of QRHJ decoction, and the IP-related genes were from the Genecards database. Cytoscape software was used to establish the interaction network. R package clusterProfiler was utilized for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The molecular docking analysis of target proteins and the corresponding active pharmaceutical ingredients in the core position of the interaction network was conducted. Then, molecular dynamics (MD) simulations of a potential active substance and its key targets were performed. The binding efficiency of EGFR and luteolin, HIF1A and diosgenin was detected by cellular thermal shift assay (CETSA), and protein expression was measured by Western blot. CCK-8 was used to detect cell activity., Results: A total of 153 active ingredients, 127 targets and 362 IP-related genes were obtained. KEGG enrichment analysis identified IP-related signaling pathways including HIF-1 signaling pathway and TNF signaling pathway. The two key components luteolin and diosgenin stably bound to the key targets EGFR and HIF1A. Cell experiments further showed that EGFR and luteolin, HIF1A and diosgenin bound to exert anti-fibrotic effects., Conclusion: As an active ingredient of QRHJ decoction, luteolin and diosgenin may exert therapeutic effect on IP through binding to the key target EGFR and HIF1A. This work initially revealed the key molecular mechanism of QRHJ decoction in IP treatment and offered theoretical evidence., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Li et al.)

Introduction: Eosinophilic granulomatosis with polyangiitis (eGPA) is a necrotising vasculitis of small and medium calibre vessels, which affects mostly patients in their fourth to sixth decade of life, and it is a very uncommon aetiology for pulmonary fibrosis., Clinical Case: A Hispanic 72-year-old female patient presents with a history of lower extremities pain, paraesthesia, oedema, and occasional macroscopic haematuria. During her hospitalisation, the patient presents, and images showed findings compatible with pulmonary fibrosis and alveolar haemorrhage, which require a biopsy, establishing the diagnosis of an eGPA., Discussion: eGPA is a low-incidence autoimmune vasculitis, with a high number of phenotypes which explain the broad clinical spectrum, but recent advances has helped to understand the physiopathology and its link with other conditions like pulmonary fibrosis., Conclusion: Early diagnosis and management of this condition is mandatory because it is the only factor that change the outcome of the patients., Competing Interests: The authors declare no have any conflict of interest., (© 2024 The Mediterranean Journal of Rheumatology (MJR).)

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research., Competing Interests: ST declares consultancy and speaker’s fees from Roche and Boehringer Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tomassetti, Ciani, Luzzi, Gori, Trigiani, Giuntoli, Lavorini, Poletti, Ravaglia, Torrego, Maldonado, Lentz, Annunziato, Maggi, Rossolini, Pollini, Para, Ciurleo, Casini, Rasero, Bartoloni, Spinicci, Munavvar, Gasparini, Comin, Cerinic, Peired, Henket, Ernst, Louis, Corhay, Nardi and Guiot.)

Patients with lung cancer complicated by interstitial pneumonia (IP) often lose treatment options early owing to acute exacerbation of IP concerns. Carbon-ion radiotherapy (CIRT) can provide superior tumor control and low toxicity at high dose concentrations. We conducted a retrospective analysis of the efficacy and tolerability of a single-fraction CIRT using 50 Gy for IP-complicated lung cancer. The study included 50 consecutive patients treated between April 2013 and September 2022, whose clinical stage of lung cancer (UICC 7th edition) was 1A:1B:2A:2B = 32:13:4:1. Of these, 32 (64%) showed usual interstitial pneumonia patterns. With a median follow-up of 23.5 months, the 3-year overall survival (OS), cause-specific survival, and local control rates were 45.0, 75.4, and 77.8%, respectively. The median lung V5 and V20 were 10.0 and 5.2%, respectively (mean lung dose, 2.6 Gy). The lung dose, especially lung V20, showed a strong association with OS ( p = 0.0012). Grade ≥ 2 pneumonia was present in six patients (13%), including two (4%) with suspected grade 5. CIRT can provide a relatively safe and curative treatment for patients with IP-complicated lung cancer. However, IP increases the risk of severe radiation pneumonitis, and further studies are required to assess the appropriate indications.

Purposes: Secondary spontaneous pneumothorax (SSP) is occasionally observed in elderly patients suffering from diffuse lung diseases. The purpose of this study was to analyze the outcomes of surgical treatment of SSP patients with chronic lung diseases., Methods: In total, 242 patients who underwent surgery for spontaneous pneumothorax at Chiba University Hospital from January 2006 to October 2016 were included in this study. The patients' records were reviewed retrospectively for data on their background, surgical treatment, morbidity, mortality, and recurrence., Results: Of the spontaneous pneumothorax cohort, primary spontaneous pneumothorax (PSP) accounted for 144 patients. Among the 98 patients with SSP, 57 cases were caused by chronic obstructive pulmonary disease (COPD) and 21 were caused by interstitial pneumonia (IP). The postoperative complication rate was 19.3% in the COPD group, 42.9% in the IP group, and 11.1% in the PSP group. The recurrence rate was 5.3% in the COPD group, 28.6% in the IP group, and 21.5% in the PSP group., Conclusions: The morbidity and recurrence were comparable between PSP and SSP cases with COPD, whereas these values were unfavorable in SSP cases with IP compared with PSP ones. Surgical intervention should be carefully considered in SSP patients with IP.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with rapidly progressive evolution and an unfavorable outcome. Nintedanib (NTD) is an antifibrotic drug that has been shown to be effective in slowing down the progression of the disease. The aim of our study was to examine the efficacy, especially in terms of the functional decline, and the safety profile of NTD in patients treated with the recommended dose and subjects who reduced or suspended the therapy due to the occurrence of adverse reactions., Methods: We conducted a real-life retrospective study based on the experience of NTD use in two centers between 2015 and 2022. Clinical data were evaluated at baseline, at 6 and 12 months after the NTD introduction in the whole population and in subgroups of patients who continued the full-dose treatment, at a reduced dosage, and at the discontinuation of treatment. The following data were recorded: the demographic features, IPF clinical features, NTD therapeutic dosage, tolerability and adverse events, pulmonary function tests (PFTs), the duration of treatment upon discontinuation, and the causes of interruption., Results: There were 54 IPF patients who were included (29.6% females, with a median (IQR) age at baseline of 75 (69.0-79.0) years). Twelve months after the introduction of the NTD therapy, 20 (37%) patients were still taking the full dose, 11 (20.4%) had reduced it to 200 mg daily, and 15 (27.8%) had stopped treatment. Gastrointestinal intolerance predominantly led to the dose reduction (13.0%) and treatment cessation (20.4%). There were two deaths within the initial 6 months (3.7%) and seven (13.0%) within 12 months. Compared to the baseline, the results of the PFTs remained stable at 6 and 12 months for the entire NTD-treated population, except for a significant decline in the DLCO (% predicted value) at both 6 (38.0 ± 17.8 vs. 43.0 ± 26.0; p = 0.041) and 12 months (41.5 ± 15.3 vs. 44.0 ± 26.8; p = 0.048). The patients who continued treatment at the full dose or a reduced dosage showed no significant differences in the FVC and the DLCO at 12 months. Conversely, those discontinuing the NTD exhibited a statistically significant decline in the FVC (% predicted value) at 12 months compared to the baseline (55.0 ± 13.5 vs. 70.0 ± 23.0; p = 0.035)., Conclusions: This study highlights the functional decline of the FVC at 12 months after the NTD initiation among patients discontinuing therapy but not among those reducing their dosage.