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Abstract Background Anti-Ro-52 antibodies have been associated with interstitial lung disease (ILD) in various autoimmune diseases. However, their role in ILD among patients with idiopathic inflammatory myopathies (IIMs) is relatively underexplored. This study aimed to investigate the association between anti-Ro-52 antibodies and the occurrence of ILD in individuals with IIMs. Methods This retrospective observational study included 604 patients who underwent myositis autoantibody testing between July 2018 and January 2021 at our hospital and were diagnosed with either IIMs or IIM-mimics. Comparative analyses were conducted between IIMs and IIM-mimics, as well as within the IIM group between cases with and without ILD. Logistic regression or Firth’s logistic regression analyses were employed to assess the risk of ILD development in different IIM subgroups and myositis antibody categories. Results This study included 190 patients with IIM and 414 patients with IIM-mimics. Patients with IIM demonstrated higher incidence of ILD, concurrent autoimmune disease, and a greater likelihood of various myositis autoantibodies when compared to the IIM-mimics group. Within the IIM patient cohort, those with ILD exhibited a later age of onset of IIM, an increased mortality rate, and a more frequent presence of anti-aminoacyl-tRNA synthetase (ARS) antibodies compared to those without ILD. The presence of any myositis-specific antibody (MSA) was associated with a six-fold increased risk of ILD, while dual positivity for MSA and anti-Ro-52 antibodies conferred a twenty-fold risk. Anti-ARS antibodies carried a 14-fold increased risk of ILD, which escalated to 38-fold in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies. Anti-Ro-52 antibodies alone increased the risk eight-fold. Conclusions Among patients with IIM, the presence of ILD was linked to higher mortality. Certain autoantibodies, notably anti-ARS and anti-Ro-52 antibodies, were associated with an increased risk of ILD. The greatest risk of ILD was observed in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies.

Lung cancer remains a formidable health challenge due to its high mortality and morbidity rates. Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancer cases, with small cell lung cancer (SCLC) accounting for the remainder. Both NSCLC and SCLC cells express receptor tyrosine kinases, which may be overexpressed or mutated in lung cancer, leading to increased activation. The c-Met receptor tyrosine kinase, crucial for cell transformation and tumor growth, invasion, and metastasis, became the focus of our study. We used an E1B55KD-deleted, replication-selective oncolytic adenovirus (Ad.What), driven by the c-Met promoter, targeting lung cancer cells with c-Met overexpression, thus sparing normal cells. Previous studies have shown the enhanced antitumor efficacy of oncolytic adenoviruses when combined with chemotherapeutic agents. We explored combining rapamycin, a selective mTOR inhibitor with promising clinical trial outcomes for various cancers, with Ad.What. This combination increased infectivity by augmenting the expression of coxsackievirus and adenovirus receptors and αV integrin on cancer cells and induced autophagy. Our findings suggest that combining a c-Met promoter-driven oncolytic adenovirus with rapamycin could be an effective lung cancer treatment strategy, offering a targeted approach to exploit lung cancer cells’ vulnerabilities, potentially marking a significant advancement in managing this deadly disease.

Abstract Tracheopathia osteochondroplastica (TO) is a rare and benign condition. It typically manifests as multiple osteocartilaginous nodules in the submucosa of the central airway. TO‐related clinical symptoms and physical signs are nonspecific. The bronchoscopic examination is helpful in establishing the diagnosis. Treatment for TO is mostly conservative and symptom‐oriented. The prognosis of TO is generally good, although cases of associated airway stenosis have been reported. In this case report, we describe the clinical, imaging, and histological features, and videoed bronchoscopic findings, of a middle‐aged male patient with incidentally diagnosed TO.

Abstract Alveolar macrophages (AMs) are the drivers of pulmonary cytokine storm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to investigate clinical–regulatory factors for the entrance protein of SARS-CoV-2, angiotensin–converting enzyme 2 (ACE2) in AMs. Human AMs were collected from 56 patients using bronchoalveolar lavage. ACE2 expression in AMs was positively correlated with smoking pack-year (Spearman’s r = 0.347, P = 0.038). In multivariate analysis, current smoking was associated with increased ACE2 in AMs (β-coefficient: 0.791, 95% CI 0.019–1.562, P = 0.045). In vitro study, ex-vivo human AMs with higher ACE2 were more susceptible to SARS-CoV-2 pseudovirus (CoV-2 PsV). Treating human AMs using cigarette smoking extract (CSE) increases the ACE2 and susceptibility to CoV-2 PsV. CSE did not significantly increase the ACE2 in AMs of reactive oxygen species (ROS) deficient Cybb–/– mice; however, exogenous ROS increased the ACE2 in Cybb–/– AMs. N-acetylcysteine (NAC) decreases ACE2 by suppressing intracellular ROS in human AMs. In conclusion, cigarette smoking increases the susceptibility to SARS-CoV-2 by increasing ROS–induced ACE2 expression of AMs. Further investigation into the preventive effect of NAC on the pulmonary complications of COVID-19 is required.

Abstract Amiodarone is a commonly used antiarrhythmic agent but exhibits potential pulmonary toxicity. In this case series, we describe the clinical, radiographic, and histologic manifestations of three patients who developed interstitial lung disease (ILD) following amiodarone treatment for variable lengths of time with different dosages. The presentations on computed tomographic images and in pulmonary pathology differed among the three patients. All three had immediate discontinuation of amiodarone and received treatment with systemic corticosteroids. One patient eventually died from ventilator‐associated pneumonia after an initial improvement. The other two patients recovered well but later experienced ILD recurrence following brief re‐exposure to amiodarone. Through this case series, we aim to demonstrate the variable features of amiodarone‐related ILD, and highlight the importance of timely amiodarone cessation and avoiding re‐exposure to prevent the progression and recurrence of ILD.

Background: A comprehensive study of respiratory pathogens was conducted in an area with a low prevalence of COVID-19 among the adults quarantined at a tertiary hospital. Methods: From March to May 2020, 201 patients suspected lower respiratory tract infection (LRTI) were surveyed for etiologies by multiplex polymerase chain reaction (PCR: FilmArray TM Respiratory Panel) test combination with cultural method, viral antigen detection and serologic surveys. Results: Total 201 patients tested with FilmArray TM Respiratory Panel were enrolled, of which 68.2% had sputum bacterial culture, 86.1% had pneumococcus and Legionella urine antigen test. Their median age was 72.0 year-old with multiple comorbidities, and 11.4% were nursing home residents. Bacteria accounted for 59.7% of identified pathogens. Atypical pathogens were identified in 31.3% of total pathogens, of which viruses accounted for 23.9%. In comparison to patients with bacterial infection, patients with atypical pathogens were younger (median= 77.2 vs 67.1, years, P = 0.017) and had shorter length of hospital (8.0 vs 4.5, days, P = 0.007). Conclusions: Patients with LRTI caused by atypical pathogens was indistinguishable from those with bacterial pathogens by clinical manifestations or biomarkers. Multiplex PCR providing rapid diagnosis of atypical pathogens enhance patient care and decision making when rate of sputum culture sampling was low in quarantine ward during pandemic.

Mucin-1 is a multi-functional glycoprotein expressed by type II alveolocytes and may be detectable in the circulation following pulmonary fibrosis. The prognostic utility of baseline pre-treatment blood levels of mucin-1 in patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotics has not yet been fully established. We retrospectively studied a cohort of patients (from two hospitals) with IPF who were receiving pirfenidone for >12 weeks. Baseline blood mucin-1 levels were measured via sandwich enzyme-linked immunosorbent assays. We investigated the performance of mucin-1 levels in longitudinally predicting the risks of acute exacerbation of IPF (AE-IPF) and severe adverse outcomes (SAO), including lung transplantation and death. Seventy patients were included; 20 developed AE-IPF; and 31 had SAO during the follow-up period. Patients with baseline mucin-1 levels ≥2.5 ng/mL had enhanced risks of AE-IPF (adjusted hazard ratio [aHR], 14.07; 95% confidence interval [CI], 4.26–46.49) and SAO within 2 years (aHR, 7.87; 95% CI, 2.86–21.70) and anytime during the follow-up (aHR, 4.68; 95% CI, 2.11–10.39). The risks increased across subgroups with increasing mucin-1 levels. Patients in the “mucin-1 ≥ 2.5” group also exhibited an accelerated decline in DLCO. This study supports baseline blood mucin-1 levels as a biomarker for IPF that predicts adverse outcomes during pirfenidone treatment.

Background/Purpose: Early detection and timely quarantine measures are necessary to control disease spread and prevent nosocomial outbreaks of Coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the impact of a quarantine strategy on patient safety and quality of care. Methods: This retrospective cohort study enrolled patients admitted to the quarantine ward in a tertiary hospital in southern Taiwan. The incidence and causes of acute critical illness, including clinical deterioration and unexpected complications during the quarantine period, were reviewed. Further investigation was performed to identify risk factors for acute critical illness during quarantine. Results: Of 320 patients admitted to the quarantine ward, more than two-thirds were elderly, and 37.8% were bedridden. During the quarantine period, 68 (21.2%) developed acute critical illness, which more commonly occurred among patients older than 80 years and with a bedridden status, nasogastric tube feeding, or dyspnea symptoms. Bedridden status was an independent predictor of acute critical illness. Through optimization of sampling for COVID-19 and laboratory schedules, both the duration of quarantine and the proportion of acute critical illness among bedridden patients during quarantine exhibited a decreasing trend. There was no COVID-19 nosocomial transmission during the study period. Conclusion: The quarantine ward is a key measure to prevent nosocomial transmission of COVID-19 but may carry a potential negative impact on patient care and safety. For patients with multiple comorbidities and a bedridden status, healthcare workers should remain alert to rapid deterioration and unexpected adverse events during quarantine.

Background Organising pneumonia (OP) has variable clinical and radiographic presentations and unstandardised treatments. Most patients with OP have favourable outcomes, but some develop respiratory insufficiency, experience recurrence or die. In this study we investigated the impact of computed tomographic (CT) patterns and extent of OP on the diagnostic and therapeutic management that patients received, and that on the therapeutic response and prognosis (particularly the risk of respiratory insufficiency and death). Methods We retrospectively studied 156 patients with OP followed at our hospital between 2010 and 2021. The diagnosis was confirmed histologically and verified by multidisciplinary specialists. We performed Firth's logistic regression to determine the relationship between CT features and aetiologies, management and outcomes including the risk of severe disease (defined as the need for supplemental oxygen or mechanical ventilation). We conducted Kaplan–Meier analyses to assess survival differences. Results Patients exhibiting multilobe involvement or mixed patterns, or both, were more likely to have secondary OP and receive immunosuppressants. Higher proportions of these patients experienced recurrence. Compared to patients with single-lobe involvement and single-pattern, they also had an enhanced risk of severe disease (the adjusted odds ratio for patients who simultaneously had multilobe involvement and mixed patterns was 27.64; 95% confidence interval 8.25–127.44). Besides, these patients had decreased survival probabilities. Conclusion Different CT features of OP impact patients’ management and prognosis. When treating patients with OP exhibiting multilobe involvement or mixed patterns, or both, it is important to identify the possible causative aetiology and follow closely for adverse outcomes.

Background Fibrosing interstitial lung diseases (fILD) are potentially fatal with limited therapeutic options and no effective strategies to reverse fibrogenesis. Myofibroblasts are chief effector cells in fibrosis that excessively deposit collagen in the pulmonary interstitium and lead to progressive impairment of gaseous exchange. Methods Plasma and lung specimens from patients with fILD were applied for detecting pentraxin 3 (PTX3) abundance by ELISA and Immunohistochemistry. Masson's trichrome and Sirius red stains and hydroxyproline assay were performed for assessing collagen accumulation in the lungs of bleomycin‐exposed conditional Ptx3‐deficient and PTX3‐neutralizing antibody (αPTX3i)‐treated mice. Downstream effectors including signaling pathways and fibrotic genes were examined for assessing CD44‐involved PTX3‐induced fibrosis in HFL1 and primary mouse fibroblasts. Results PTX3 was upregulated in the lungs and plasma of bleomycin‐exposed mice and correlated with disease severity and adverse outcomes in fILD patients. Decreased collagen accumulation, attenuation of alveolar fibrosis and fibrotic markers, and improved lung function were observed in bleomycin‐exposed conditional Ptx3‐deficient mice. PTX3 activates lung fibroblasts to differentiate towards migrative and highly collagen‐expressing myofibroblasts. Lung fibroblasts with CD44 inactivation attenuated the PI3K‐AKT1, NF‐κB, and JNK signaling pathways and fibrotic markers. αPTX3i mimic‐based therapeutic studies demonstrated abrogation of the migrative fibroblast phenotype and myofibroblast activation in vitro. Notably, αPTX3i inhibited lung fibrosis, reduced collagen deposition, increased mouse survival, and improved lung function in bleomycin‐induced pulmonary fibrosis. Conclusions The present study reveals new insights into the involvement of the PTX3/CD44 axis in fibrosis and suggests PTX3 as a promising therapeutic target in fILD patients.

Abstract Background Nintedanib is effective for treating idiopathic pulmonary fibrosis (IPF), but some patients may exhibit a suboptimal response and develop on-treatment acute exacerbation (AE-IPF), hepatic injury, or mortality. It remains unclear which patients are at risk for these adverse outcomes. Methods We analysed the demographic and clinical data, baseline plasma levels of Krebs von den Lungen-6 (KL-6) and surfactant protein A (SPA), and longitudinal clinical courses of a real-world cohort of IPF patients who received nintedanib ≥ 14 days between March 2017 and December 2020. Cox proportional-hazards regression, subdistribution hazards regression, and sensitivity analyses were performed to investigate the association between baseline predictors and AE-IPF, mortality, and nintedanib-related hepatic injury. The relationship between baseline predictors and pulmonary function decline was determined. Results Fifty-seven patients were included, of whom 24 (42%) developed hepatic injury, 20 (35%) had AE-IPF, and 16 (28%) died on-treatment. A baseline plasma KL-6 level ≥ 2.5 ng/mL, and diffusion capacity for carbon monoxide (DLCO)

Abstract Patients with chronic bronchiectasis are susceptible to various respiratory complications. In this report, however, we describe a 53‐year‐old male with chronic bronchiectasis who developed extensive but asymptomatic jejuno‐ileal pneumatosis intestinalis. The patient did not have preceding pneumothorax or pneumomediastinum, and he did not receive cytotoxic or immunosuppressive therapy. Nor did he exhibit any clinical or radiographic evidence of intestinal ischaemia, obstruction or infection. Mucosal defects, due to his severe diarrhoea relating to the prolonged anti‐pseudomonal antibiotic treatment for his lungs, and the intestinal luminal pressure fluctuation, resulting from his exacerbated cough and from his frequent abdominal straining during defecation, were considered to have precipitated the condition. Following conservative treatment, the patient recovered well. In addition to adverse respiratory events, clinicians managing patients with bronchiectasis should also be alert to such an unusual extrapulmonary complication, because either neglecting the condition or unnecessary exploratory surgery may lead to hazardous outcomes.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Relapsing polychondritis (RP) is a rare autoimmune disorder, characterized by the inflammation of cartilaginous structures and proteoglycan‐rich tissues. Due to its rarity and the notoriously variable presentations, the diagnosis of RP could be challenging. We report an unusual case of RP with isolated tracheal involvement and very non‐specific symptoms of exertional dyspnoea and dry cough. The initial chest radiograph showed long‐segment narrowing of the trachea, and the computed tomography of the chest revealed thickened cartilaginous walls of the trachea, while the posterior membranous portion was spared. The tracheal narrowing was readily observed under bronchoscopy. The patient was treated with oral prednisolone. Although the subsequent course was transiently complicated by an episode of severe Pneumocystis jirovecii pneumonia with acute respiratory distress syndrome, the patient overall responded well to systemic corticosteroid therapy. No new symptoms developed during a two‐year follow‐up.

Lymphocytic interstitial pneumonia (LIP) is an uncommon interstitial lung disease that is characterized by an interstitial infiltrate of lymphoplasmacytic cells. While idiopathic LIP appears to be extremely rare, most reported cases of LIP have been associated with coexisting immune derangements, particularly autoimmune diseases such as Sjögren's syndrome. In this report, we describe the presentation of LIP in a patient with underlying mixed connective tissue disease. Keywords: Lymphocytic interstitial pneumonia, Mixed connective tissue disease

Primary effusion lymphoma (PEL) is a rare subtype of non‐Hodgkin's lymphoma. PEL is closely related in pathogenesis to human herpesvirus 8 (HHV‐8) and typically occurs in patients with significant immunodeficiency. Cases of PEL in patients without either HIV infection or transplantation have been reported from HHV‐8‐endemic areas, but very rarely from the Asia‐Pacific region. In this case series, we describe the clinical and immunohistochemical presentations of four patients in southern Taiwan who were diagnosed with HHV‐8‐related PEL. All four patients were HIV‐negative and had not received organ transplantation. To our knowledge, this is the first authentic report of HIV‐unrelated PEL from the ethnically Chinese population. Considering the non‐specific clinical manifestations, the pivotal roles of specific assays for correct diagnosis, and the dismal prognosis of PEL, it is important for clinicians to include PEL as one of the differential diagnosis when approaching HIV‐uninfected patients with unexplained exudative body cavity effusion.

In this report, we describe an unusual manifestation of pulmonary alveolar proteinosis (PAP). The patient is a 43‐year‐old non‐smoking female without underlying hematologic or auto‐immune disorder. Her initial presentation included non‐specific respiratory symptoms (exertional dyspnoea and cough), an unremarkable physical examination, a mild elevation in her serum level of lactate dehydrogenase, a mild impairment in the diffusion capacity for carbon monoxide but a normal spirometry, and multiple ground‐glass opacities with a “crazy‐paving” pattern predominantly in upper lung zones on her chest radiographic images. PAP was diagnosed histologically. PAP commonly occurs in males with smoking history, and tends to affect the lung parenchyma diffusely or, as in auto‐immune PAP, lower lobes predominantly. Upper‐lobe predominant PAP, particularly in a non‐smoking female, is rare. This report would add PAP to the list of differential diagnosis for upper‐lung ground‐glass opacities. A review on the relevant literature is also included in the discussion.

A 48-year-old nonsmoking male noodle maker presented with cough, exertional dyspnea, and intermittent hemoptysis for several weeks. There was no fever, chest pain, skin eruption, arthralgia, or weight loss. His medical, travel, and family histories were unremarkable. Considering his presentations and frequent occupational exposure to organic (sometimes moldy) particulates, as well as the radiographic findings (peripheral ill-defined ground-glass opacities with an internal crazy-paving pattern) (Figures 1A and 1B), infectious or exposure-induced atypical pneumonitis (including subacute hypersensitivity or eosinophilic pneumonia) was suspected initially. However, empirical antimicrobial and corticosteroid treatments were ineffective. Autoantibodies (including antineutrophil cytoplasmic antibodies) were all negative. Diagnostic BAL recovered blood-tinged fluid with nonspecific mixed-type cellularity. Initial cultures (blood, sputum, and lavage fluid), PCR tests, nasopharyngeal multiplex microbial assays, and serological tests indicated no microbial (including severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) infection. Video-assisted thoracoscopic wedge biopsy was performed. Tissue cultures yielded no pathogen. The histological examination revealed many tumor emboli in the pulmonary arterioles, with associated infarction and alveolar hemorrhage involving the nearby parenchyma (Figure 2A). The tumor cells exhibited poorly differentiated spindle-shaped or epithelioid appearances with minimal necrosis and frequent mitosis and were immunohistochemically positive for CD31 (cluster of differentiation 31), CD34, and Fli-1 (friend leukemia integration 1) (Figures 2B-2E) but negative for CK (cytokeratin), CK7, TTF1 (thyroid transcription factor 1), P40, myogenin, MDM2 (mouse double minute 2 homolog), and CDK4 (cyclin dependent kinase 4). Semiquantitative estimation of Ki-67 index was 35% (Figure 2F). Subsequent computed tomography angiography (Figure 1C, arrow) and transthoracic echocardiography (Figure 1D, marked) identified the main tumor in the right atrium. Contrast-enhanced abdominal computed tomography excluded intraabdominal lesions. Grade 3 stage IV right atrial angiosarcoma with pulmonary metastases was diagnosed. The patient then received chemotherapy with pazopanib and paclitaxel. Although he experienced clinical and radiographic improvement (Figure 1E) after the treatments, he died of metastasis-related severe intracranial hemorrhage 6 months later. Some images in this article were presented in a poster at the 2021 Annual Congress of the Taiwan Society of Pulmonary and Critical Care Medicine (1). [ABSTRACT FROM AUTHOR]

This study tests our hypothesis that patients with chronic obstructive pulmonary disease (COPD) have an increased risk of traumatic brain injury (TBI).In this nationwide retrospective cohort study, we used a subset of Taiwan's National Health Insurance Research Database, involving 1 million randomly selected beneficiaries. Patients with newly diagnosed COPD between 2000 and 2008 were identified. They were subgrouped as 'COPDAE+' (if they had severe acute exacerbation of COPD during the follow-ups) or 'COPDAE-' (if they had no acute exacerbation), and were frequency matched with randomly selected subjects without COPD (the 'non-COPD' group). Baseline differences were balanced by the inverse probability of treatment weighting based on the propensity score. For each patient, the risk of TBI during the subsequent 5 years was determined. The competing risk of death was controlled.We identified 3734 patients in 'COPDAE+', and frequency matched them with 11,202 patients in 'COPDAE-' and 11,202 subjects in 'non-COPD'. Compared with those in 'non-COPD', patients in 'COPDAE+' and 'COPDAE-' had an increased risk of TBI: the adjusted HR for 'COPDAE+' was 1.50, 95% CI 1.31 to 1.73, and that for 'COPDAE-' was 1.21, 95% CI 1.09 to 1.34. The highest risk was observed in the 'COPDAE+' group that aged <65 (the adjusted HR was 1.92; 95% CI 1.39 to 2.64).COPD has been linked to complications beyond the respiratory system. In this study we showed that COPD is associated with an increased risk of TBI. [ABSTRACT FROM AUTHOR]