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Background: Immune-related pneumonitis (irP) is one of the most important immune-related adverse events caused by immune checkpoint inhibitors (ICIs). After corticosteroid therapy irP frequently relapses, which can interfere with cancer therapy. However, risk factors for irP relapse are unknown. Methods: This study was a follow-up analysis of a phase II study that evaluated 56 patients with grade ≥ 2 irP treated with oral prednisolone, 1 mg/kg/day, tapered over 6 weeks. Clinical factors including patient characteristics, blood test findings, and response to prednisolone therapy were assessed to identify risk factors for irP relapse using the Fine–Gray test. Results: Among 56 patients with irP, 22 (39.3%) experienced irP relapse after 6 weeks of prednisolone therapy during the follow-up observation period. Radiographic organising pneumonia (OP) pattern and duration to irP onset ≥ 100 days from ICI initiation were determined to be significant risk factors for irP relapse in a multivariate Fine–Gray test (hazard ratio [HR] = 3.17, 95% CI 1.37–7.32, p = 0.007, and HR = 2.61, 95% CI 1.01–6.74, p = 0.048, respectively). Other patient characteristics, blood test findings, irP severity, and response to prednisolone therapy were not associated with irP relapse. Conclusions: In irP patients treated with 6-week prednisolone tapering therapy, OP pattern and duration to irP onset ≥ 100 days were associated with relapse risk. Assessment of the risk factors for irP relapse will be helpful for irP management. [ABSTRACT FROM AUTHOR]

Ovine pulmonary adenocarcinoma (OPA) is an important viral-induced neoplasia in sheep caused by exogenous Jaagsiekte sheep retrovirus (exJSRV). Coinfection of exJSRV and Maedi-Visna virus (MVV) is reported in OPA cases, but its worldwide distribution and significance on lung pathology is not yet completely understood. This study aimed to investigate the MVV coinfection rate in 82 exJSRV-related OPA cases, and their pathological effects on lung parenchyma in slaughtered sheep in Transylvania (Romania). On gross examination, classical form of OPA was identified in 92.7%; no changes consisting with MVV interstitial pneumonia were identified in the included cases. The most common histological type of OPA was acinar (58.5%) and the myxoid growths were found in 18 cases. The exJSRV and MMV coinfection rate in examined sheep was 47.6% (39/82). The assessment of perineoplastic areas from coinfected animals, revealed interstitial lymphoplasmacytic infiltrates in all cases, lymphoid hyperplasia in 60.6% cases (20/33) and fibromuscular hyperplasia in 63.7% (21/33). This is the first report providing new data on distribution of OPA coexisting with MVV infection in slaughtered sheep in Romania. We consider that the OPA and MVV coinfection may play an important role on the severity of ovine chronic pulmonary diseases and further studies are needed to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Purpose: We describe a case of intraocular inflammation and palpable purpura in a patient with Pasteurella multocida pneumonia. Methods: A 75-year-old pseudophakic woman with type-2 diabetes and chronic obstructive pulmonary disease complained of lower limb palpable purpura and right vision loss of five-day duration. On admission, right visual acuity was hand motion. Slit-lamp examination disclosed severe conjunctival and ciliary injection, corneal oedema, 3-mm hypopyon with heavy fibrin accumulation and blood clots, and synechiae to the IOL. Results: Chest computed tomography revealed interstitial pneumonia. Sputum culture yielded P. multocida. Amoxicillin/clavulanic tablets (1 g × 3/daily) and topical and systemic steroids were given. Later on, fluorescein angiography showed multiple choroidal lesions bilaterally. With the above-mentioned therapy, there was full recovery of the skin, lung, and eye lesions. Conclusion: This report emphasizes that P. multocida infection should be considered in patients with intraocular inflammation, palpable purpura, and interstitial pneumonia. A multidisciplinary approach is necessary for a correct diagnosis and management. [ABSTRACT FROM AUTHOR]

Abstract Background Immune-related pneumonitis (irP) is one of the most important immune-related adverse events caused by immune checkpoint inhibitors (ICIs). After corticosteroid therapy irP frequently relapses, which can interfere with cancer therapy. However, risk factors for irP relapse are unknown. Methods This study was a follow-up analysis of a phase II study that evaluated 56 patients with grade ≥ 2 irP treated with oral prednisolone, 1 mg/kg/day, tapered over 6 weeks. Clinical factors including patient characteristics, blood test findings, and response to prednisolone therapy were assessed to identify risk factors for irP relapse using the Fine–Gray test. Results Among 56 patients with irP, 22 (39.3%) experienced irP relapse after 6 weeks of prednisolone therapy during the follow-up observation period. Radiographic organising pneumonia (OP) pattern and duration to irP onset ≥ 100 days from ICI initiation were determined to be significant risk factors for irP relapse in a multivariate Fine–Gray test (hazard ratio [HR] = 3.17, 95% CI 1.37–7.32, p = 0.007, and HR = 2.61, 95% CI 1.01–6.74, p = 0.048, respectively). Other patient characteristics, blood test findings, irP severity, and response to prednisolone therapy were not associated with irP relapse. Conclusions In irP patients treated with 6-week prednisolone tapering therapy, OP pattern and duration to irP onset ≥ 100 days were associated with relapse risk. Assessment of the risk factors for irP relapse will be helpful for irP management.

Although rapidly progressive glomerulonephritis (RPGN) is the main renal phenotype of microscopic polyangiitis (MPA), we aim to clarify the clinical features of slowly progressive MPA. This retrospective observational study included 12 patients diagnosed with MPA in our hospital between January 2012 and February 2022. We investigated the differences in surrogate markers, rate of decline of estimated glomerular filtration rate (eGFR) between the slowly progressive and rapidly progressive MPA groups. Of the 12 patients with MPA, 3 (25.0%) had slowly progressive MPA: MPA within 30% decrease in eGFR 3 months pretreatment, all of whom developed RPGN during the course. Patients with slowly progressive MPA had lower levels of C-reactive protein, myeloperoxidase anti-neutrophil cytoplasmic antibodies, and interleukin-6; higher levels of sialylated carbohydrate antigen KL-6. Slowly progressive MPA is not uncommon in our hospital. A linear relationship was found between slower rate of eGFR decline and lower surrogate markers of disease activity. Some MPA cases have slowly progressive glomerulonephritis leading to RPGN, which may be clinically characterized by low disease activity. It may be useful to measure myeloperoxidase anti-neutrophil cytoplasmic antibody in chronic kidney disease with concomitant urinary abnormalities to diagnose MPA with slowly progressive glomerulonephritis.

Abstract An 84‐year‐old man with a history of progressive interstitial pneumonia presented to our department with lung cancer (cT2aN0M0‐IB) in right S6. Moreover, computed tomography revealed progressive diffuse pulmonary ossification in the bilateral lower pulmonary lobes. S6 segmentectomy was performed via video‐assisted thoracoscopic surgery. It was difficult to divide the intersegmental plane using a stapler because of severe fibrosis and pulmonary ossification with bone marrow formation. Pulmonary ossification may be an important finding for surgical planning because of severe fibrosis or inflammation associated with severe lung condition. We suggest that the surgical indications and approaches for such cases should be reconsidered because pulmonary ossification can be associated with severe lung conditions.

Abstract Background Interstitial pneumonia and emphysema may complicate patients with lung cancer. However, clinical significance of trivial and mild pulmonary abnormalities remains unclear. In this study, we aimed to investigate whether trivial and mild interstitial pneumonia and emphysema, in addition to their advanced forms, impact the prognosis and lead to acute exacerbation of interstitial pneumonia (AEIP) in patients with lung cancer. Methods This retrospective cohort study was conducted at a tertiary hospital and included patients with lung cancer. Computed tomography images were evaluated using the interstitial lung abnormality (ILA) score for interstitial pneumonia, which included no ILA, equivocal ILA, ILA, interstitial lung disease (ILD), and the Goddard score for emphysema. Cox analyses were performed using the ILA and Goddard scores as the main explanatory variables, adjusting for multiple covariates. Results Among 1,507 patients with lung cancer, 1,033 had no ILA, 160 had equivocal ILA, 174 had ILA, and 140 had ILD. In total, 474 patients (31.5%) exhibited interstitial pneumonia and 638 (42.3%) showed emphysema. The log-rank trend test showed that survival probability was significantly better in patients with no ILA, followed by those with equivocal ILA, ILA, and ILD (P

Abstract Background Rapamycin has been extensively utilized for coating coronary artery stents to reduce the occurrence of restenosis, yet there has been limited research on the potential harms of rapamycin-eluting stents. Herein, We report a case of eosinophilia and interstitial pneumonia caused by a cobalt-based alloy stent eluted with rapamycin. Case presentation The patient was admitted due to fever, cough, and expectoration symptoms. Previously, the patient had undergone a procedure of percutaneous coronary stent implantation in our hospital’s cardiology department, which led to a gradual rise in blood eosinophil count. This time, the eosinophil count was higher than the previous admission. A chest CT scan revealed multiple flocculent density increases in both lungs and bronchiectasis. The rapamycin-eluting stents may have caused eosinophilia and interstitial pneumonia, which improved after administering corticosteroids. A systematic review of relevant literature was conducted to summarize the characteristics of interstitial pneumonia caused by drug-eluting stents. Conclusion Paclitaxel, everolimus, zotarolimus, and rapamycin are the types of drugs that can lead to drug-eluting stents, and because of the rarity of their onset, clinical doctors must be precise and prompt in diagnosing suspected cases to avoid misdiagnosis and delayed treatment.

Abstract Neonatal pulmonary hemorrhage is a late manifestation of various diseases. Premature delivery and low body weight are frequently observed as high-risk factors, characterized by acute onset, rapid progression, and high mortality rates. Pulmonary hemorrhage caused by cytomegalovirus infection in newborns with normal immune function is a rare occurrence. This case report focuses on a term neonate with normal birth weight who presented solely with nasal obstruction shortly after birth. However, 4 days after birth, the newborn experienced a sudden onset of blood gushing from both the mouth and nasal cavity. The patient was diagnosed with gastrointestinal bleeding, neonatal pneumonia and neonatal lung consolidation. And he was discharged after ten days of symptomatic treatment. However, upon returning home, the patient experienced a sudden onset of bleeding from the mouth and nose, leading to his untimely demise. Subsequent autopsy revealed the presence of pulmonary hemorrhage in newborn, which presented as interstitial pneumonia. The cause of pulmonary hemorrhage is cytomegalovirus infection. This case emphasizes the importance of pediatricians enhancing their skills in differentiating pulmonary hemorrhage, especially from cytomegalovirus pneumonia.

Purpose: The diagnosis of progressive fibrosing interstitial lung disease (PF-ILD) using computed tomography (CT) is an important medical practice in respiratory care, and most imaging findings for this disease have been obtained with inspiratory CT. It is possible that some characteristic changes in respiration may be seen in normal and diseased lung in PF-ILD, which may lead to a new understanding of the pathogenesis of interstitial pneumonia, but it has never been examined. In this study, we collected and selected inspiratory and expiratory CT scans performed in pure PF-ILD cases, and evaluated the volumes of diseased and normal lung separately by manual detection and 3-dimensional volumetry to characterize the dynamic features of PF-ILD. Materials and methods: Cases were collected retrospectively from a total of 753 inspiratory and expiratory CT scans performed at our hospital over a 3-year period. Sixteen cases of pure PF-ILD, excluding almost all other diseases, were included. We measured their diseased, normal, and the whole lung volumes manually and evaluated the correlation of their values and their relationship with respiratory function tests (FVC, FVC%-predicted, and DLCO%-predicted). Results: The relative expansion rate of the diseased lung is no less than that of the normal lung. The "Expansion volume of total lung" divided by the "Expansion volume of normal lung" was found to be significantly associated with DLCO%-predicted abnormalities (p = 0.0073). Conclusion: The diseased lung in PF-ILD retained expansion capacity comparable to the normal lung, suggesting a negative impact on respiratory function. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the surgical outcomes and postoperative survival prognostic factors of intractable secondary spontaneous pneumothorax. Methods: A total of 95 patients who underwent thoracoscopic surgery for intractable secondary spontaneous pneumothorax between April 2010 and March 2020 were included in this study. These patients were classified into interstitial pneumonia and non-interstitial pneumonia groups, and a comparative study was performed on surgical outcomes and postoperative survival prognostic factors. Results: There was no difference in the 1-year overall survival rate between the two groups. However, the 3-year overall survival rate was significantly lower in the interstitial pneumonia group than in the non-interstitial pneumonia group. The differences in short-term surgical outcomes (persistent air leakage, postoperative complications, etc.) were not significant between the two groups. Univariate analysis revealed that the drainage period, the development of postoperative complications, and recurrence were significant independent postoperative survival prognostic factors for all cases. Postoperative complications were the only associated postoperative survival prognostic factor for interstitial pneumonia pneumothorax in the multivariate analysis. Conclusion: The development of postoperative complications can cause poor postoperative survival prognosis of intractable secondary spontaneous pneumothorax due to interstitial pneumonia. [ABSTRACT FROM AUTHOR]

Background: Interstitial pneumonia and emphysema may complicate patients with lung cancer. However, clinical significance of trivial and mild pulmonary abnormalities remains unclear. In this study, we aimed to investigate whether trivial and mild interstitial pneumonia and emphysema, in addition to their advanced forms, impact the prognosis and lead to acute exacerbation of interstitial pneumonia (AEIP) in patients with lung cancer. Methods: This retrospective cohort study was conducted at a tertiary hospital and included patients with lung cancer. Computed tomography images were evaluated using the interstitial lung abnormality (ILA) score for interstitial pneumonia, which included no ILA, equivocal ILA, ILA, interstitial lung disease (ILD), and the Goddard score for emphysema. Cox analyses were performed using the ILA and Goddard scores as the main explanatory variables, adjusting for multiple covariates. Results: Among 1,507 patients with lung cancer, 1,033 had no ILA, 160 had equivocal ILA, 174 had ILA, and 140 had ILD. In total, 474 patients (31.5%) exhibited interstitial pneumonia and 638 (42.3%) showed emphysema. The log-rank trend test showed that survival probability was significantly better in patients with no ILA, followed by those with equivocal ILA, ILA, and ILD (P < 0.001). After adjustment, the ILA and Goddard scores remained significant variables for increased hazard ratios (HR) for mortality: no ILA (HR, 1.00: reference), equivocal ILA (HR, 1.31; 95% confidence interval [CI], 1.18–1.46; P < 0.001), ILA (HR, 1.71; 95% CI, 1.39–2.12; P < 0.001), ILD (HR, 2.24; 95% CI, 1.63–3.09; P < 0.001), and Goddard score (HR, 1.03; 95% CI, 1.01–1.06; P < 0.010). Moreover, both scores were associated with increased cause-specific HRs for AEIP. Conclusion: Our results revealed that approximately one-third of patients with lung cancer had interstitial pneumonia when incorporating trivial and mild cases. Because interstitial pneumonia and emphysema, ranging from trivial to severe, significantly impact mortality and AEIP in patients with lung cancer, we should identify even trivial and mild cases of these pulmonary abnormalities among patients with lung cancer in addition to the advanced ones. [ABSTRACT FROM AUTHOR]

Background: Rapamycin has been extensively utilized for coating coronary artery stents to reduce the occurrence of restenosis, yet there has been limited research on the potential harms of rapamycin-eluting stents. Herein, We report a case of eosinophilia and interstitial pneumonia caused by a cobalt-based alloy stent eluted with rapamycin. Case presentation: The patient was admitted due to fever, cough, and expectoration symptoms. Previously, the patient had undergone a procedure of percutaneous coronary stent implantation in our hospital's cardiology department, which led to a gradual rise in blood eosinophil count. This time, the eosinophil count was higher than the previous admission. A chest CT scan revealed multiple flocculent density increases in both lungs and bronchiectasis. The rapamycin-eluting stents may have caused eosinophilia and interstitial pneumonia, which improved after administering corticosteroids. A systematic review of relevant literature was conducted to summarize the characteristics of interstitial pneumonia caused by drug-eluting stents. Conclusion: Paclitaxel, everolimus, zotarolimus, and rapamycin are the types of drugs that can lead to drug-eluting stents, and because of the rarity of their onset, clinical doctors must be precise and prompt in diagnosing suspected cases to avoid misdiagnosis and delayed treatment. [ABSTRACT FROM AUTHOR]

Neonatal pulmonary hemorrhage is a late manifestation of various diseases. Premature delivery and low body weight are frequently observed as high-risk factors, characterized by acute onset, rapid progression, and high mortality rates. Pulmonary hemorrhage caused by cytomegalovirus infection in newborns with normal immune function is a rare occurrence. This case report focuses on a term neonate with normal birth weight who presented solely with nasal obstruction shortly after birth. However, 4 days after birth, the newborn experienced a sudden onset of blood gushing from both the mouth and nasal cavity. The patient was diagnosed with gastrointestinal bleeding, neonatal pneumonia and neonatal lung consolidation. And he was discharged after ten days of symptomatic treatment. However, upon returning home, the patient experienced a sudden onset of bleeding from the mouth and nose, leading to his untimely demise. Subsequent autopsy revealed the presence of pulmonary hemorrhage in newborn, which presented as interstitial pneumonia. The cause of pulmonary hemorrhage is cytomegalovirus infection. This case emphasizes the importance of pediatricians enhancing their skills in differentiating pulmonary hemorrhage, especially from cytomegalovirus pneumonia. [ABSTRACT FROM AUTHOR]

Ovine gammaherpesvirus 2 (OvGHV2), is a Macavirus and the cause of sheep-associated malignant catarrhal fever (SA-MCF), in which sheep are the asymptomatic reservoir hosts. Susceptible mammalian populations infected by OvGHV2 may develop clinical SA-MCF or subclinical infections. All members of the Macavirus genus known to be associated with MCF are collectively referred to as the MCF virus (MCFV) complex. This report describes the occurrence of subclinical OvGHV2-related infections in free-ranging wild boars (Sus scrofa) from southern Brazil. Specific body organs (n = 14) and biological samples (nasal and oral swabs; n = 17) were collected from 24 asymptomatic wild boars from a conservation unit located within the Central-eastern mesoregion of Paraná State. Organs were processed to observe histopathological patterns suggestive of diseases of domestic animals; only pulmonary samples were used in an immunohistochemical assay designed to detect MCFV tissue antigens. Furthermore, all samples were submitted to molecular assays designed to detect the OvGHV2 tegument protein gene. Viral-induced pneumonia was diagnosed in two wild boars; one of these contained OvGHV2 DNA, with MCFV antigens identified in the other. Additionally, MCFV tissue antigens were detected within pulmonary epithelial cells of the lungs with and without pulmonary disease. Collectively, OvGHV2 was detected in 37.5% (9/24) of all wild boars, with detection occurring in the organs of 57.1% (8/14) wild boars and the oral cavity of one animal. These results demonstrated that these wild boars were subclinically infected by OvGHV2, and that infection produced typical pulmonary alterations. In addition, the detection of OvGHV2 within the oral cavity of one wild boar may suggest that this animal may be a potential disseminator of this pathogen to susceptible animal populations, including livestock and wildlife, acting as a possible bridge host for OvGHV2. Furthermore, infection by OvGHV2 probably occurred due to incidental contact with asymptomatic sheep maintained within the surrounding rural areas and not within the conservation units. [ABSTRACT FROM AUTHOR]

Objectives: To compare the characteristics and prognosis of patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) with pleuroparenchymal fibroelastosis (PPFE) with those of patients with nodular/bronchiectatic (NB) and fibrocavitary (FC) NTM-PD. Methods: This multicenter, retrospective, observational study enrolled 32 patients with NTM-PPFE (median age: 70.5 years, 15 females) from six institutions in Japan from January 2003 to December 2018. Their clinical characteristics and response to therapy were compared with age- and sex-matched cohorts of patients with noncavitary NB and cavitary NB/FC NTM-PD. Results: Patients with NTM-PPFE had a lower body mass index and a higher standard NTM-PD therapy initiation rate than patients with other NTM-PD types. Sputum culture conversion rates were comparable between groups; however, patients with NTM-PPFE had a higher incidence of treatment-related adverse events, including optic neuropathy associated with high-dose ethambutol therapy, lower percent predicted forced vital capacity values, higher serum Krebs von den Lungen-6 (KL-6) levels, and poorer treatment outcomes than the other groups. Cox regression revealed that NTM-PPFE was an independent risk factor for death/pneumothorax (adjusted hazard ratio: 35.3, 95% confidence interval: 3.90-4692). Conclusion: NTM-PPFE is a unique NTM-PD phenotype with a poorer prognosis than the NB and FC phenotypes.

Ovine pulmonary adenocarcinoma (OPA) is an important viral-induced neoplasia in sheep caused by exogenous Jaagsiekte sheep retrovirus (exJSRV). Coinfection of exJSRV and Maedi-Visna virus (MVV) is reported in OPA cases, but its worldwide distribution and significance on lung pathology is not yet completely understood. This study aimed to investigate the MVV coinfection rate in 82 exJSRV-related OPA cases, and their pathological effects on lung parenchyma in slaughtered sheep in Transylvania (Romania). On gross examination, classical form of OPA was identified in 92.7%; no changes consisting with MVV interstitial pneumonia were identified in the included cases. The most common histological type of OPA was acinar (58.5%) and the myxoid growths were found in 18 cases. The exJSRV and MMV coinfection rate in examined sheep was 47.6% (39/82). The assessment of perineoplastic areas from coinfected animals, revealed interstitial lymphoplasmacytic infiltrates in all cases, lymphoid hyperplasia in 60.6% cases (20/33) and fibromuscular hyperplasia in 63.7% (21/33). This is the first report providing new data on distribution of OPA coexisting with MVV infection in slaughtered sheep in Romania. We consider that the OPA and MVV coinfection may play an important role on the severity of ovine chronic pulmonary diseases and further studies are needed to confirm this hypothesis.

An 84‐year‐old man with a history of progressive interstitial pneumonia presented to our department with lung cancer (cT2aN0M0‐IB) in right S6. Moreover, computed tomography revealed progressive diffuse pulmonary ossification in the bilateral lower pulmonary lobes. S6 segmentectomy was performed via video‐assisted thoracoscopic surgery. It was difficult to divide the intersegmental plane using a stapler because of severe fibrosis and pulmonary ossification with bone marrow formation. Pulmonary ossification may be an important finding for surgical planning because of severe fibrosis or inflammation associated with severe lung condition. We suggest that the surgical indications and approaches for such cases should be reconsidered because pulmonary ossification can be associated with severe lung conditions. [ABSTRACT FROM AUTHOR]

Background: Community acquired pneumonia (CAP) is an important subject in pulmonary medicine and chest imaging plays a major role in the diagnosis and chest x ray (CXR) historically are the image of choice in the workup. Aims and objectives: to provide the role of chest X-ray (CXR) in diagnosis of pneumonia. Materials and Methods: This study which involves 185 cases of high clinical probability of CAP investigated by CXR and several patterns of infiltrates has been detected mainly lobar pneumonia followed by interstitial infiltrates then lobular and bronchopneumonic pattern. Chest x ray is not only a tool for diagnosis but also can be utilized in the follow up for resolution or development of complications. Results: CXR is a good modality for pneumonia diagnosis in which lobar pattern of infiltrate was the most common type 82 patient (44.3%), followed by interstitial pattern which was 57 patients (30.8%), then bronchopneumonia pattern 21 patient (11.3%) and lobular pattern 20 patient (10.8%). Conclusions and Recommendations: Chest x ray plays a major role in diagnosis of pneumonia, it can provide information about any structural pulmonary diseases , exclude alternative diagnoses and even giving an idea about the possible underlying pathogen and hence the antibiotic that preferred to be use; so we recommend to use CXR as an initial modality of choice in cases of suspected pneumonia.

Aim. To study the clinical and histological profile of lung tissue in patients with persistent pulmonary disease, respiratory symptoms and CT findings after SARS-CoV-2 infection. Materials and methods. The study included 15 patients (7 females and 8 males) with a mean age of 57.7 years. All patients underwent laboratory tests, chest computed tomography, echocardiography, and pulmonary function tests. Pulmonary tissue and bronchoalveolar lavage samples were obtained by fibrobronchoscopy, transbronchial forceps (2 patients), and lung cryobiopsy (11 patients); open biopsy was performed in 2 patients. Cellular composition, herpesvirus DNA, SARS-CoV-2, Mycobacterium tuberculosis complex, galactomannan optical density index, and bacterial and fungal microflora growth were determined in bronchoalveolar lavage. SARS-CoV-2 was also identified in samples from the nasal mucosa, throat and feces using a polymerase chain reaction. Results. The results showed no true pulmonary fibrosis in patients recovered from SARS-CoV-2 infection with persistent respiratory symptoms, functional impairment, and CT findings after SARS-CoV-2 infection. The observed changes comply with the current and/or resolving infection and inflammatory process. Conclusion. Thus, no true pulmonary fibrosis was found in patients after SARS-CoV-2 infection with persistent respiratory symptoms, functional impairment, and CT findings. The observed changes comply with the current and/or resolving infection and inflammatory process.

Simple Summary: Lung cancer patients are frequently complicated by various respiratory diseases during their course. In particular, interstitial pneumonia and chronic obstructive pulmonary disease are often associated with lung cancer due to their common pathogenesis, and acute exacerbations of these diseases can be fatal. Therefore, it is important to select a therapy that is less likely to induce acute exacerbations of interstitial pneumonia and chronic obstructive pulmonary disease. Furthermore, lung cancer patients are at high risk of developing or reactivating pulmonary tuberculosis triggered by pharmacotherapy and often struggle with the diagnosis and treatment of tuberculosis complicated by lung cancer. This review summarizes the current evidence regarding pharmacotherapy for lung cancer patients with interstitial pneumonia, chronic obstructive pulmonary disease, and pulmonary tuberculosis and discusses future prospects. Non-small cell lung cancer (NSCLC) patients are often complicated by other respiratory diseases, including interstitial pneumonia (IP), chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB), and the management of which can be problematic. NSCLC patients with IP sometimes develop fatal acute exacerbation induced by pharmacotherapy, and the establishment of a safe treatment strategy is desirable. For advanced NSCLC with IP, carboplatin plus nanoparticle albumin-bound paclitaxel is a relatively safe and effective first-line treatment option. Although the safety of immune checkpoint inhibitors (ICIs) for these populations remains controversial, ICIs have the potential to provide long-term survival. The severity of COPD is an important prognostic factor in NSCLC patients. Although COPD complications do not necessarily limit treatment options, it is important to select drugs with fewer side effects on the heart and blood vessels as well as the lungs. Active TB is complicated by 2–5% of NSCLC cases during their disease course. Since pharmacotherapy, especially ICIs, reportedly induces the development of TB, the possibility of developing TB should always be kept in mind during NSCLC treatment. To date, there is no coherent review article on NSCLC with these pulmonary complications. This review article summarizes the current evidence and discusses future prospects for treatment strategies for NSCLC patients complicated with IP, severe COPD, and TB. [ABSTRACT FROM AUTHOR]

Indium lung is an occupational lung disease caused by exposure to indium-tin-oxide (ITO) dust. Compared to other occupational lung diseases, indium lung has a shorter latency period and the respiratory status continues to worsen even after exposure to the work environment improves. Paraseptal emphysema which affects mainly the subpleural area is seen on chest images obtained via computed tomography (CT), regardless of the smoking history. However, the pathogenesis of emphysema in indium lung is still unclear. Therefore, we re-evaluated the pathology of three previously reported cases of indium lung. Paraseptal emphysema was observed in both smokers and nonsmokers. Obstructive respiratory impairment worsened over time in the cases with paraseptal emphysema. Many alveolar walls were destroyed independent of the presence or absence of emphysetamous changes or fibrosis. Moreover, bronchiolitis was found to be less common in indium lung than in asbestosis (the most common occupational lung disease) or common cases of chronic obstructive pulmonary disease caused by smoking. It has been shown that ITO causes protease anti-protease imbalance, oxidant-antioxidant imbalance, and continuous, abnormal inflammation (the three major causes of emphysema). In addition, nano-sized ITO is less likely to be trapped in the upper airways and may easily reach the subpleural alveoli. Furthermore, ITO may continue to cause sustained tissue injury at the alveolar level potentially resulting in emphysema. Further studies are needed to elucidate the detailed pathogenesis of indium lung by comparing it with other occupational lung diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Interstitial pneumonia (IP) represents a significant prognostic comorbidity in patients diagnosed with non-small-cell lung cancer (NSCLC). Even if treatment for lung cancer proves effective, the occurrence of an acute exacerbation in pre-existing IP can pose a substantial risk to patient survival. Consequently, it is crucial to opt for a therapy that minimizes the likelihood of triggering an acute IP exacerbation. Evidence is limited regarding pharmacotherapy for advanced NSCLC with a low risk of triggering the exacerbation of pre-existing IP, but KRASG12C inhibitors may be a potential treatment option for NSCLC with comorbid IP. In this review article, we discuss the promise and prospects of molecular-targeted therapy, particularly KRASG12C inhibitors, which gained little attention as a treatment for NSCLC with comorbid IP. Non-small-cell lung cancer (NSCLC) with comorbid interstitial pneumonia (IP) is a population with limited treatment options and a poor prognosis. Patients with comorbid IP are at high risk of developing fatal drug-induced pneumonitis, and data on the safety and efficacy of molecularly targeted therapies are lacking. KRAS mutations have been frequently detected in patients with NSCLC with comorbid IP. However, the low detection rate of common driver gene mutations, such as epidermal growth factor receptor and anaplastic lymphoma kinase, in patients with comorbid IP frequently results in inadequate screening for driver mutations, and KRAS mutations may be overlooked. Recently, sotorasib and adagrasib were approved as treatment options for advanced NSCLC with KRASG12C mutations. Although patients with comorbid IP were not excluded from clinical trials of these KRASG12C inhibitors, the incidence of drug-induced pneumonitis was low. Therefore, KRASG12C inhibitors may be a safe and effective treatment option for NSCLC with comorbid IP. This review article discusses the promise and prospects of molecular-targeted therapies, especially KRASG12C inhibitors, for NSCLC with comorbid IP, along with our own clinical experience. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to explore the factors influencing the treatment failure of high-flow nasal cannula (HFNC) therapy in patients with interstitial pneumonia (IP) complicated by respiratory failure. PATIENTS AND METHODS: A total of 158 patients with IP and respiratory failure treated with HFNC in our hospital from January 2020 to August 2023 were selected as the study population. Based on treatment efficacy, they were categorized into the HFNC treatment failure group and the HFNC treatment success group. Clinical data were compared between the two groups. Multiple logistic regression analysis was employed to identify independent factors influencing treatment failure, and the predictive value of these factors for HFNC treatment failure was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: After 7 days of HFNC treatment, among the 158 patients with IP and respiratory failure, 25 (15.8%) declared treatment failure, while the remaining 133 (84.2%) showed treatment success. Patients in the HFNC treatment failure group had significantly higher age, duration of IP, pre-treatment respiratory rate, C-reactive protein (CRP), and controlling nutritional status (CONUT) scores compared to the HFNC treatment success group. The PaO2/FiO2 ratio, left ventricular ejection fraction, and Glasgow Coma Scale (GCS) were significantly lower in the HFNC treatment failure group (p<0.05). Multiple logistic regression analysis revealed that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores were independent factors influencing HFNC treatment failure in patients with IP and respiratory failure (p<0.05). Lower PaO2/FiO2 ratio and GCS scores, and higher CRP and CONUT scores were associated with an increased risk of HFNC treatment failure. ROC curve analysis indicated that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores in patients with IP and respiratory failure had a high predictive value for HFNC treatment failure (p<0.05). CONCLUSIONS: The HFNC failure rate in patients with IP and respiratory failure is 15.8%. Pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores are independent factors associated with HFNC treatment failure and warrant clinical attention. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important infectious diseases for the pig industry worldwide. The disease was firstly reported in 1987 and became endemic in many countries. Since then, outbreaks caused by strains of high virulence have been reported several times in Asia, America and Europe. Interstitial pneumonia, microscopically characterised by thickened alveolar septa, is the hallmark lesion of PRRS. However, suppurative bronchopneumonia and proliferative and necrotising pneumonia are also observed, particularly when a virulent strain is involved. This raises the question of whether the infection by certain strains results in an overstimulation of the proinflammatory response and whether there is some degree of correlation between the strain involved and a particular pattern of lung injury. Thus, it is of interest to know how the inflammatory response is modulated in these cases due to the interplay between virus and host factors. This review provides an overview of the macroscopic, microscopic, and molecular pathology of PRRSV-1 strains in the lung, emphasising the differences between strains of different virulence. [ABSTRACT FROM AUTHOR]

This study was aimed to identification and detection of Mycoplasma dispar by conventional real-time polymerase chain reaction (PCR) assays followed by routine hematoxylin & eosin technique to further confirmation of Mycoplasma species related to the lesions observed in diseased calves. Ten samples of infected lung tissue were gathered and fixed in 10% neutral buffered formalin and handled for making a microscopic slide after confirming Mycoplasma dispar infection by PCR. Histopathological examination of the lung revealed two types of pneumonia; chronic suppurative pneumonia in 60% of the cases and 40% of diffuse interstitial pneumonia. Mycoplasma dispar was confirmed based on genetic analysis. Slemani/2018 field isolate showed 99.84% homologies with four reference isolates of Mycoplasma dispar in NCBI GenBank. Phylogenetic analysis indicated a close relation to Mycoplasma ovipneumoniae, Mycoplasma hyopneumoniae, and Mycoplasma flocculare, often isolated from sheep and goats. Therefore, further study is crucial to identify Iraqi livestock's circulating Mycoplasma species related to respiratory diseases. [ABSTRACT FROM AUTHOR]

Chunxiang Li,1,&ast; Yingbin Lian,1,&ast; Yaoshen Lin,1 Zhihua Li2 1Department of Integrative Medicine Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, 362000, People’s Republic of China; 2Department of Oncology, Zhangzhou Second Hospital, Zhangzhou, Fujian, 363199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihua Li, Department of Oncology, Zhangzhou Second Hospital, No. 35, Ziwei Road, Shima Town, Longhai District, Zhangzhou, Fujian, 363199, People’s Republic of China, Tel +86-13459666448, Email zhihua_leeee@163.comObjective: 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.Keywords: Qing Run Hua Jie decoction, interstitial pneumonia, network pharmacology, molecular docking, molecular dynamics

Abstract Background Previous studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF). Methods Fifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared. Results Of the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids. Conclusion Our findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive.

Simple Summary: Patients with lung cancer complicated by interstitial pneumonia (IP) often lose treatment options early because of concerns about acute exacerbation of IP. Carbon-ion radiotherapy (CIRT) is expected to provide both superior tumor control and low toxicity owing to its superior dose concentration; however, it is not yet a well-established therapy. In this study, we confirmed that 50 Gy single-fraction CIRT can be performed even in IP-complicated lung cancer with acceptable efficacy and tolerability. Lung dose is a significant predictor of overall survival, indicating the need for further efforts to reduce lung dose. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Previous studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF). Methods: Fifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared. Results: Of the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids. Conclusion: Our findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive. [ABSTRACT FROM AUTHOR]

Interstitial pneumonia is the most common and serious secondary lesion of dermatomyositis. In some cases, patients may develop severe acute pneumonia that can quickly progress to respiratory failure, resulting in high mortality rates. A 57-year-old woman with dermatomyositis and interstitial pulmonary fibrosis experienced severe hypoxemia due to pulmonary infection. Despite receiving various treatments after entering the intensive care unit (ICU), such as anti-infection therapy, lung recruitment, prone position ventilation, sedative and muscle relaxation, the patient’s oxygen saturation continued to decline. Electrical impedance tomography (EIT) monitoring revealed that prone position could not improve ventilation homogeneity. However, the patient’s ventilation/perfusion (V/Q) matching significantly improved 10 min after initiation of supine position ventilation combined with inhalation of nitric oxide (iNO). The patient’s PaO2/FiO2 (P/F) ratio increased from 86 mmHg to 150 mmHg at 30 min post-treatment. iNO treatment continued for 2 days. Then the patient’s condition improved and she was successfully weaned off the ventilator with rigorous monitoring and symptomatic care. The implementation of mechanical ventilation combined with iNO therapy rapidly improved V/Q matching and oxygenation in a patient with hypoxemia caused by dermatomyositis complicated with interstitial pneumonia. This approach successfully avoided the need for invasive extracorporeal membrane oxygenation (ECMO) support.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important infectious diseases for the pig industry worldwide. The disease was firstly reported in 1987 and became endemic in many countries. Since then, outbreaks caused by strains of high virulence have been reported several times in Asia, America and Europe. Interstitial pneumonia, microscopically characterised by thickened alveolar septa, is the hallmark lesion of PRRS. However, suppurative bronchopneumonia and proliferative and necrotising pneumonia are also observed, particularly when a virulent strain is involved. This raises the question of whether the infection by certain strains results in an overstimulation of the proinflammatory response and whether there is some degree of correlation between the strain involved and a particular pattern of lung injury. Thus, it is of interest to know how the inflammatory response is modulated in these cases due to the interplay between virus and host factors. This review provides an overview of the macroscopic, microscopic, and molecular pathology of PRRSV-1 strains in the lung, emphasising the differences between strains of different virulence.

Abstract Background The prognosis of patients with lung cancer accompanied by interstitial pneumonia is poorer than that of patients with lung cancer but without interstitial pneumonia. Moreover, the available therapeutic interventions for lung cancer patients with interstitial pneumonia are limited. Therefore, a new treatment strategy for these patients is required. The aim of the present study was to investigate the pathophysiological relationship between interstitial pneumonia and lung cancer and explore potential therapeutic agents. Methods A novel hybrid murine model of lung cancer with interstitial pneumonia was established via bleomycin-induced pulmonary fibrosis followed by orthotopic lung cancer cell transplantation into the lungs. Changes in tumor progression, lung fibrosis, RNA expression, cytokine levels, and tumor microenvironment in the lung cancer with interstitial pneumonia model were investigated, and therapeutic agents were examined. Additionally, clinical data and samples from patients with lung cancer accompanied by interstitial pneumonia were analyzed to explore the potential clinical significance of the findings. Results In the lung cancer with interstitial pneumonia model, accelerated tumor growth was observed based on an altered tumor microenvironment. RNA sequencing analysis revealed upregulation of the hypoxia-inducible factor 1 signaling pathway. These findings were consistent with those obtained for human samples. Moreover, we explored whether ascorbic acid could be an alternative treatment for lung cancer with interstitial pneumonia to avoid the disadvantages of hypoxia-inducible factor 1 inhibitors. Ascorbic acid successfully downregulated the hypoxia-inducible factor 1 signaling pathway and inhibited tumor progression and lung fibrosis. Conclusions The hypoxia-inducible factor 1 pathway is critical in lung cancer with interstitial pneumonia and could be a therapeutic target for mitigating interstitial pneumonia-mediated lung cancer progression.

Ovine gammaherpesvirus 2 (OvGHV2), is a Macavirus and the cause of sheep-associated malignant catarrhal fever (SA-MCF), in which sheep are the asymptomatic reservoir hosts. Susceptible mammalian populations infected by OvGHV2 may develop clinical SA-MCF or subclinical infections. All members of the Macavirus genus known to be associated with MCF are collectively referred to as the MCF virus (MCFV) complex. This report describes the occurrence of subclinical OvGHV2-related infections in free-ranging wild boars (Sus scrofa) from southern Brazil. Specific body organs (n = 14) and biological samples (nasal and oral swabs; n = 17) were collected from 24 asymptomatic wild boars from a conservation unit located within the Central-eastern mesoregion of Paraná State. Organs were processed to observe histopathological patterns suggestive of diseases of domestic animals; only pulmonary samples were used in an immunohistochemical assay designed to detect MCFV tissue antigens. Furthermore, all samples were submitted to molecular assays designed to detect the OvGHV2 tegument protein gene. Viral-induced pneumonia was diagnosed in two wild boars; one of these contained OvGHV2 DNA, with MCFV antigens identified in the other. Additionally, MCFV tissue antigens were detected within pulmonary epithelial cells of the lungs with and without pulmonary disease. Collectively, OvGHV2 was detected in 37.5% (9/24) of all wild boars, with detection occurring in the organs of 57.1% (8/14) wild boars and the oral cavity of one animal. These results demonstrated that these wild boars were subclinically infected by OvGHV2, and that infection produced typical pulmonary alterations. In addition, the detection of OvGHV2 within the oral cavity of one wild boar may suggest that this animal may be a potential disseminator of this pathogen to susceptible animal populations, including livestock and wildlife, acting as a possible bridge host for OvGHV2. Furthermore, infection by OvGHV2 probably occurred due to incidental contact with asymptomatic sheep maintained within the surrounding rural areas and not within the conservation units.

Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 T cell influx into the cerebrospinal fluid. Our data show that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure.

In recent years, immunotherapy has made a breakthrough in the field of non-small cell lung cancer, reshaping the pattern of lung cancer treatment. However, with the wide application of immunotherapy in clinical practice, immune-related adverse events have attracted increasing attention. Immune pneumonia, as one of the immune-related toxic side effects of greatest concern, affects the treatment process and curative effect and can be a threat to life in serious cases. Given that immune pneumonia has a complicated pathogenesis and diverse clinical manifestations, strengthening the understanding of immune pneumonia is urgently needed. The treatment of immune pneumonia is limited, and additional therapeutic medicines are still awaiting exploration. Therefore, this paper summarizes the progress of the research on immune pneumonia in the treatment of non-small cell lung cancer.

Abstract Introduction Secondary spontaneous pneumothorax (SSP) occurs as one of the complications associated with interstitial pneumonia (IP). Chest drainage is performed when there is a large volume of air in the pleural space. Notably, SSP with IP (SSP‐IP) is frequently not curable by chest drainage only. A digital drainage system (DDS) provides an objective evaluation of air leakage and maintains a pre‐determined negative pressure, compared to an analog drainage system (ADS). Few studies have reported the effectiveness of DDS in the treatment of SSP‐IP. This study aimed to assess the usefulness of DDS for SSP‐IP. Methods This retrospective study included patients with SSP‐IP who had undergone chest drainage. We reviewed the included patients' medical records, laboratory data, computed tomography findings, and pulmonary function data. Results DDS was used in 24 patients and ADS in 49 patients. The mean duration of chest drainage was 11.4 ± 1.9 days in the DDS group and 14.2 ± 1.3 days in the ADS group, which was not significantly different (p = 0.218). Surgery, pleurodesis, and/or factor XIII administration were performed in 40 patients. Additionally, five (20.8%) patients in the DDS group and nine (18.4%) in the ADS group had a recurrence of pneumothorax within 4 weeks (p = 1.000). One patient (14%) in the DDS group and six (12.2%) in the ADS group (p = 0.414) were cured of pneumothorax but later died. Conclusion DDS did not demonstrate a significant difference in the shortening of chest drainage duration. Further study is needed to validate the results of this study.

This report involves a 54-year-old female patient diagnosed with diffuse large B-cell lymphoma who developed interstitial pneumonia (IP) during treatment. The patient presented to the ward with enlarged lymph nodes in the neck and was treated with the standard regimen, which included rituximab, cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (R-CDOP regimen). After 3 cycles, the treatment was assessed as effective. However, following the 4th cycle, the patient experience shortness of breath after physical activity. A repeat lung computer tomography indicated IP, which completely recovered after receiving “full coverage” treatment. Subsequently, the patient underwent 2 cycles of cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (CDOP), followed by local radiotherapy. Currently, the patient is now being followed up with regular reviews.

Abstract Background The diagnostic accuracy and safety of transbronchial lung cryobiopsy (TBLC) via a flexible bronchoscope under sedation compared with that of surgical lung biopsy (SLB) in the same patients is unknown. Methods Retrospectively the data of fifty-two patients with interstitial lung diseases (median age: 63.5 years; 21 auto-antibody positive) who underwent TBLC followed by SLB (median time from TBLC to SLB: 57 days) was collected. The samples from TBLC and SLB were randomly labelled to mask the relationship between the two samples. Diagnosis was made independently by pathologists, radiologists, and pulmonary physicians in a stepwise manner, and a final diagnosis was made at multidisciplinary discussion (MDD). In each diagnostic step the specific diagnosis, the diagnostic confidence level, idiopathic pulmonary fibrosis (IPF) diagnostic guideline criteria, and treatment strategy were recorded. Results Without clinical and radiological information, the agreement between the histological diagnoses by TBLC and SLB was 42.3% (kappa [κ] = 0.23, 95% confidence interval [CI]: 0.08–0.39). However, the agreement between the TBLC-MDD and SLB-MDD diagnoses and IPF/non-IPF diagnosis using the two biopsy methods was 65.4% (κ = 0.57, 95% CI: 0.42–0.73) and 90.4% (47/52), respectively. Out of 38 (73.1%) cases diagnosed with high or definite confidence at TBLC-MDD, 29 had concordant SLB-MDD diagnoses (agreement: 76.3%, κ = 0.71, 95% CI: 0.55–0.87), and the agreement for IPF/non-IPF diagnoses was 97.4% (37/38). By adding the pathological diagnosis, the inter-observer agreement of clinical diagnosis improved from κ = 0.22 to κ = 0.42 for TBLC and from κ = 0.27 to κ = 0.38 for SLB, and the prevalence of high or definite diagnostic confidence improved from 23.0% to 73.0% and from 17.3% to 73.0%, respectively. Of all 383 TBLC performed during the same period, pneumothorax occurred in 5.0% of cases, and no severe bleeding, acute exacerbation of interstitial lung disease, or fatal event was observed. Conclusions TBLC via a flexible bronchoscope under deep sedation is safely performed, and the TBLC-MDD diagnosis with a high or definite confidence level is concordant with the SLB-MDD diagnosis in the same patients.

Abstract Background It is unclear whether Ureaplasma-associated pneumonia and azithromycin treatment affect the risk for bronchopulmonary dysplasia (BPD). Methods A retrospective cohort study was performed in very low birth weight (VLBW) infants who tested positive for Ureaplasma within 72 h after birth in a tertiary unit. Chest X-ray (CXR) and laboratory test were performed before and after azithromycin treatment. Multivariate logistic regression analysis was used to identify the independent association between BPD and Ureaplasma-associated pneumonia, as well as BPD and effective azithromycin treatment. Results A total of 118 infants were included in the current study, of whom 36 developed BPD (defined as supplemental oxygen needed at postmenstrual age 36 weeks or discharge). The rate of BPD was significantly higher in infants with Ureaplasma-associated pneumonia (44.6%) compared to infants with Ureaplasma colonization (17.7%, P = 0.002). After adjusting for confounders, an effective azithromycin treatment was significantly associated with reduced risk of BPD [odd ratio (OR) 0.011; 95% confidence interval (CI): 0.000–0.250), whereas Ureaplasma-associated pneumonia was not significantly associated with BPD (OR 1.835; 95% CI: 0.548–6.147). Conclusion Effective Azithromycin treatment in Ureaplasma positive VLBW infants was associated with a reduced risk of BPD.

Abstract Background Immune checkpoint blockade (ICB) elicits a strong and durable therapeutic response, but its application is limited by disparate responses and its associated immune-related adverse events (irAEs). Previously, in a murine model of lymph node (LN) metastasis, we showed that intranodal administration of chemotherapeutic agents using a lymphatic drug delivery system (LDDS) elicits stronger therapeutic responses in comparison to systemic drug delivery approaches, while minimizing systemic toxicity, due to its improved pharmacokinetic profile at the intended site. Importantly, the LN is a reservoir of immunotherapeutic targets. We therefore hypothesized that metastatic LN-targeted ICB can amplify anti-tumor response and uncouple it from ICB-induced irAEs. Methods To test our hypothesis, models of LN and distant metastases were established with luciferase expressing LM8 cells in MXH10/Mo-lpr/lpr mice, a recombinant inbred strain of mice capable of recapitulating ICB-induced interstitial pneumonia. This model was used to interrogate ICB-associated therapeutic response and immune related adverse events (irAEs) by in vivo imaging, high-frequency ultrasound imaging and histopathology. qPCR and flowcytometry were utilized to uncover the mediators of anti-tumor immunity. Results Tumor-bearing LN (tbLN)-directed CTLA4 blockade generated robust anti-tumor response against local and systemic metastases, thereby improving survival. The anti-tumor effects were accompanied by an upregulation of effector CD8T cells in the tumor-microenvironment and periphery. In comparison, non-specific CTLA4 blockade was found to elicit weaker anti-tumor effect and exacerbated ICI-induced irAEs, especially interstitial pneumonia. Together these data highlight the importance of tbLN-targeted checkpoint blockade for efficacious response. Conclusions Intranodal delivery of immune checkpoint inhibitors to metastatic LN can potentiate therapeutic response while minimizing irAEs stemming from systemic lowering of immune activation threshold.

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.