Lung adenocarcinoma discovered during the follow-up of lung-dominant connective tissue disease: a case report and literature review.

Interstitial lung disease (ILD) can lead to lung cancer, which brings great challenges to differential diagnosis and comprehensive treatment. However, the clinical features of lung-dominant connective tissue disease (LD-CTD) related ILD combined with lung cancer has not been validated. We report the case of an 80-year-old woman with LD-CTD treated regularly with nintedanib who presented progressive dyspnoea and hypoxemia after recurrent viral infections. Her chest computed tomography (CT) showed aggravated interstitial fibrosis in both lower lungs with moderate right pleural effusion. Clinicians should be alert to lung cancer in patients who are experiencing poor responsiveness to treatment or acute progression of ILD. The available literatures about the differential diagnosis of clinical manifestations, imaging, treatment and prognosis of LD-CTD are reviewed and discussed in this study.

Clinical Features and Management of Lung Cancer During Pregnancy: A Narrative Review Based on Reported Cases.

This review aims to provide a summary of the clinical characteristics and outcomes of lung cancer during pregnancy. A comprehensive literature search yielded 93 cases of lung cancer during pregnancy from 1953 to 2022, with an average maternal age of ∼34 years old. The initial symptoms reported were often nonspecific, such as cough, dyspnea, and chest pain. Cancer-related treatments, including surgery, radiotherapy, chemotherapy, and tyrosine kinase inhibitors, have shown beneficial effects on maternal outcomes. A majority of the newborns were born without malformation or diseases, but extended follow-up remains necessary. Early diagnosis of lung cancer is imperative for reducing the risks of placental and fetal metastasis and enhancing overall survival.

SERPINA1 Methylation Levels are Associated with Lung Cancer Development in Male Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The mechanism of lung cancer (LC) in male patients with chronic obstructive pulmonary disease (COPD) has not been well understood, and the early diagnosis is currently challenging. The study aimed to explore the association of DNA methylation levels with LC development in male COPD patients. Patients and Methods: A total of 147 male participants were divided into four groups, ie, COPD+LC group, COPD group, LC group, and control (CON) group. The methylation levels of human serine protease inhibitor A1 (SERPINA1) and the serum levels of inflammatory biomarkers were compared among groups. Multivariate logistic regression was performed to explore the correlation of inflammatory biomarkers and gene methylation with lung cancer combining COPD. Results: SERPINA1 methylation levels were significantly higher in the COPD+LC group than that in the COPD group and LC group, respectively (all p < 0.05). The serum levels of interleukin (IL)-1ß, IL-17, and transforming growth factor (TGF)-ß1 were significantly higher in the COPD+LC group than in the LC group (all p < 0.05). The SERPINA1 methylation levels were positively correlated with the IL-1ß levels (r = 0.5188, p = 0.0012). The AUC (area under curve) of SERPINA1 methylation for the diagnosis of LC in COPD was 0.677 (sensitivity of 52.2% and specificity of 78.2%). Conclusion: The methylation of SERPINA1 is linked to LC in patients with COPD. The SERPINA1 methylation levels were positively correlated with the IL-1ß levels. These findings may be of diagnostic value.

Surfaxin attenuates PM2.5-induced airway inflammation via restoring surfactant proteins in rats exposed to cigarette smoke.

Epidemiologic studies have shown that the fine particulate matter 2.5 (PM2.5) exaggerates chronic airway inflammation involving in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Surfactant proteins (SPs) decreases significantly related to airflow limitation and airway inflammation. However, how to restore the reduction of SPs levels in airway inflammation exposed to PM2.5 has not been well understood. In the present study, the SPs including SPA, SPB, SPC and SPD levels in bronchoalveolar lavage fluid (BALF) were detected from patients with stable COPD. Rats were exposed to cigarette smoke and PM2.5. After given with Surfaxin, the expression of SPs, protein kinase C (PKC) and tight junction protein (ZO-1) in lung tissue and the levels of C-reactive protein (CRP) and fibrinogen (FIB) in plasma was observed. The results showed that SPA, SPB and SPD were significantly lower than those of the control group (p < 0.01). PM2.5 aggravated smoking-induced airway inflammation and oxidative stress demonstrated by pathological changes of lung tissue and increased levels of CRP and PKC in vivo. PM2.5 decreased the expression of all the SPs and ZO-1, which could be significantly restored by Surfaxin. These findings indicate that Surfaxin protects the alveolar epithelium from PM2.5 in airway inflammation through increasing SPs.

Moderate to severe OSA screening based on support vector machine of the Chinese population faciocervical measurements dataset: a cross-sectional study.

OBJECTIVES: Obstructive sleep apnoea (OSA) has received much attention as a risk factor for perioperative complications and 68.5% of OSA patients remain undiagnosed before surgery. Faciocervical characteristics may screen OSA for Asians due to smaller upper airways compared with Caucasians. Thus, our study aimed to explore a machine-learning model to screen moderate to severe OSA based on faciocervical and anthropometric measurements. DESIGN: A cross-sectional study. SETTING: Data were collected from the Shanghai Jiao Tong University School of Medicine affiliated Ruijin Hospital between February 2019 and August 2020. PARTICIPANTS: A total of 481 Chinese participants were included in the study. PRIMARY AND SECONDARY OUTCOME: (1) Identification of moderate to severe OSA with apnoea-hypopnoea index 15 events/hour and (2) Verification of the machine-learning model. RESULTS: Sex-Age-Body mass index (BMI)-maximum Interincisal distance-ratio of Height to thyrosternum distance-neck Circumference-waist Circumference (SABIHC2) model was set up. The SABIHC2 model could screen moderate to severe OSA with an area under the curve (AUC)=0.832, the sensitivity of 0.916 and specificity of 0.749, and performed better than the STOP-BANG (snoring, tiredness, observed apnea, high blood pressure, BMI, age, neck circumference, and male gender) questionnaire, which showed AUC=0.631, the sensitivity of 0.487 and specificity of 0.772. Especially for asymptomatic patients (Epworth Sleepiness Scale <10), the SABIHC2 model demonstrated better predictive ability compared with the STOP-BANG questionnaire, with AUC (0.824 vs 0.530), sensitivity (0.892 vs 0.348) and specificity (0.755 vs 0.809). CONCLUSION: The SABIHC2 machine-learning model provides a simple and accurate assessment of moderate to severe OSA in the Chinese population, especially for those without significant daytime sleepiness.

A narrative review of exploring potential salivary biomarkers in respiratory diseases: still on its way.

Saliva is abundant with proteins, metabolites, DNA, and a diverse range of bacterial species. During the past two decades, saliva has emerged as a novel diagnostic and evaluation medium for several diseases. Collection of saliva samples is simple, minimally invasive, and convenient even in infants, children, and patients with anxious. Furthermore, with the development of hypersensitive techniques [e.g., microsensor arrays, enzyme-labeled immunosensors, nanoparticle-labeled immunosensors, capacitive or impedimetric immunosensors, magneto immunosensors, field effect transistor immunosensors, and surface enhanced Raman spectroscopy (SERS)], the sensitivity and accuracy of saliva diagnostic procedures have been improved. Nowadays, saliva has been used as a potential medium for several disease diagnosis and assessment, such as periodontitis, caries, cancers, diabetes mellitus, and cardiovascular diseases. Saliva has been used widely for studying microbiomics, genomics, transcriptomics, proteomics, and metabolomics of respiratory diseases, however, the use of salivary biomarkers for the diagnosis, prognosis, and monitoring of respiratory disease is still in its infancy. Herein, we review the progress of research on salivary biomarkers related to several respiratory diseases, including bronchial asthma, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), pneumonia, tuberculosis (TB), Langerhans cell histiocytosis (LCH) and cystic fibrosis (CF). Furthermore, several limitations of saliva test such as the lack of standard protocol for saliva collection and reasonable reference values for saliva test are also mentioned in this review.

Bronchial Variation: Anatomical Abnormality May Predispose Chronic Obstructive Pulmonary Disease.

Noxious particulate matter in the air is a primary cause of chronic obstructive pulmonary disease (COPD). The bronchial tree acts to filter these materials in the air and preserve the integrity of the bronchi. Accumulating evidence has demonstrated that smoking and air pollutants are the most prominent risk factors of COPD. Bifurcations in the airway may act as deposition sites for the retention of inhaled particles, however, little is known concerning the impacts of abnormalities of the bronchial anatomy in the pathogenesis of COPD. Studies have reported significant associations between bronchial variations and the symptoms in COPD. In particular, it has been shown that bronchial variations in the central airway tree may contribute to the development of COPD. In this review, we identified three common types of bronchial variation that were used to formulate a unifying hypothesis to explain how bronchial variations contribute to the development of COPD. We also investigated the current evidence for the involvement of specific genes including fibroblast growth factor 10 (Fgf10) and bone morphogenetic protein 4 (Bmp4) in the formation of bronchial variation. Finally, we highlight novel assessment strategies and opportunities for future research of bronchial variations and genetic susceptibility in COPD and comorbidities. Our data strongly highlight the role of bronchial variations in the development, complications, and acute exacerbation of COPD.

Angiotensin-(1-7) Rescues Chronic Intermittent Hypoxia-Aggravated Transforming Growth Factor-ß-Mediated Airway Remodeling in Murine and Cellular Models of Asthma.

Renin-angiotensin system (RAS) is involved in TGF-ß-mediated epithelial-to-mesenchymal transition (EMT) and is responsible for airway remodeling in refractory asthma. Obstructive sleep apnea (OSA), which affects RAS activity, is a risk factor for refractory asthma. We aimed to investigate how chronic intermittent hypoxia (IH), the main pathophysiology of OSA, exacerbates asthma and whether Ang-(1-7) protects against chronic IH-induced airway remodeling in asthma. We exposed ovalbumin (OVA)-challenged asthma mice to chronic IH and observed that chronic IH aggravated airway inflammation and collagen deposit in OVA-challenged mice. Compared with the OVA group, the OVA + chronic IH group had a lower expression level of epithelial marker E-cadherin and higher expression levels of mesenchymal markers α-smooth muscle actin and collagen IV in airway epithelia, accompanied with activation of TGF-ß/Smad pathway. These changes were reversed by the administration of Ang-(1-7). Consistently, Ang-(1-7) mitigated chronic IH-induced activation of TGF-ß-mediated EMT in lipopolysaccharide-treated bronchial epithelial cells in a dose-dependent manner, which was blocked by Ang-(1-7)-specific Mas receptor antagonist A779. Taken together, Ang-(1-7) rescued chronic IH-aggravated TGF-ß-mediated EMT to suppress airway remodeling, implying that RAS activity is involved in the mechanisms of OSA-related airway dysfunction in asthma. SIGNIFICANCE STATEMENT: OSA is a risk factor for refractory asthma. In this study, we aimed to explore the mechanisms of how OSA exacerbates refractory asthma. We found that chronic IH induces TGF-ß-mediated EMT and aggravates airway collagen deposit. We also found that Ang-(1-7) erased the aggravation of TGF-ß-mediated EMT and epithelial fibrosis upon chronic IH exposure. These findings provided new insights that the ACE2/Ang-(1-7)/Mas axis might be considered as a potential therapeutic target for patients with asthma and OSA.

AMPK/FOXO1 signaling pathway is indispensable in visfatin-regulated myosin heavy chain expression in C2C12 myotubes.

OBJECTIVE: Few studies have addressed the effects of visfatin on skeletal muscle remodeling. The aim of the study was to investigate the effects of visfatin on the expressions of myosin heavy chain (MHC) and its isoforms, the major indicator of fiber types and contractile properties of skeletal muscle. MATERIALS AND METHODS: Levels of MHC, MHC I, MHC IIa, MHC IIb, adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), p-AMPK and forkhead box protein O1 (FOXO1) were tested in visfatin-treated C2C12 myotubes. C2C12 myotubes were treated with visfatin combined with AMPK inhibitor or AMPK activator to investigate the role of AMPK in visfatin-mediated MHC expression. FOXO1 was overexpressed or knocked down in C2C12 myotubes to explore the role of FOXO1 in visfatin-mediated MHC expression. RESULTS: Compared with the vehicle group, treatment with 5 µg/ml visfatin increased the levels of total MHC and its isoforms, MHC I, MHC IIa and MHC IIb, by 1.93, 1.84, 1.80, and 1.92 folds, respectively (all p = 0,001). Visfatin suppressed AMPK phosphorylation and decreased FOXO1 expression in C2C12 myotubes. The effects of visfatin on MHC I and MHC IIa expression were canceled by AMPK activator AICAR. FOXO1 overexpression minimized the visfatin-induced upregulation of MHC I, MHC IIa and MHC IIb. The effect of AMPK activator AICAR on MHC and its isoforms expression was minimized by knockdown of FOXO1. CONCLUSIONS: The findings revealed that visfatin promoted expressions of MHC and its isoforms in C2C12 myotubes via suppressing AMPK/FOXO1 signaling pathway.

Favorable response to pemetrexed, cisplatin and bevacizumab in invasive mucinous adenocarcinoma: A case report and literature review.

Invasive mucinous adenocarcinoma (IMA) was formerly referred to as mucinous bronchioloalveolar carcinoma. The lack of effective chemotherapy and comprehensive treatment for this type of tumor poses a great challenge in clinical practice. We herein report the case of a male patient with IMA who was treated with a combination of pemetrexed (500 mg/m2), cisplatin (75 mg/m2) and bevacizumab (15 mg/kg) as first-line chemotherapy. The patient achieved significant radiological improvement with 6 courses of this regimen. After the tumor progressed, the patient again achieved marked improvement with an additional 4 courses of the same regimen. The patient survived for a total of 30 months after the first chemotherapy. Therefore, bevacizumab in combination with pemetrexed/cisplatin may be an effective strategy for the treatment of IMA. The available literature on this chemotherapy regimen was also reviewed and discussed in the present study.

[Characteristics of chronic obstructive pulmonary disease phenotypes based on high-resolution CT and the relationship with interleukin-6].

OBJECTIVE: To classify the high-resolution CT (HRCT) phenotypes of COPD, and to investigate the clinical characteristics of various phenotypes and the relationship with airway inflammation. METHODS: Chest HRCT and pulmonary function tests were performed in 84 COPD patients. The patients were classified into 3 phenotypes according to the visual HRCT findings. Exhaled breath condensate was gathered from 30 patients and the interleukin (IL)-6 level was measured by ELISA. RESULTS: The COPD patients were classified into 3 phenotypes: Phenotype A, absence of emphysema, with or without bronchial wall thickening (n = 34); Phenotype E, emphysema without bronchial wall thickening (n = 23); and Phenotype M, emphysema with bronchial wall thickening (n = 27). The 3 phenotypes of COPD showed different characteristics in several aspects. Patients with phenotype A showed a higher body mass index [(25.1 +/- 4.4) kg/m(2) vs phenotype E (22.5 +/- 4.1) kg/m(2) and phenotype M (21.3 +/- 3.4) kg/m(2), F = 6.732, P < 0.01]. The prevalence of patients with milder dyspnea was lower in phenotype A compared with others (15/34) vs phenotype E (2/23) and phenotype M (6/27), chi(2) = 9.097, P < 0.05. The patients who complained of severe expectoration in phenotype E were fewer than those in other groups (0/23) vs phenotype A (2/34) and phenotype M (4/27), chi(2) = 8.702, P < 0.05. The FEV(1)/FVC and FEV(1)% in phenotype M [(53 +/- 14)% and (51 +/- 25)%] were significantly lower as compared with those in other phenotypes [(67 +/- 11)% and (72 +/- 24)% in phenotype A, and (53 +/- 14)% and (52 +/- 26)% in phenotype E], F = 10.252, F = 6.508, P < 0.01. The ratio of inspiratory capacity to total lung capacity (IC/TLC) in phenotype A was higher [phenotype A (41 +/- 17)%, phenotype E (33 +/- 13)%, phenotype M (28 +/- 13)%, F = 5.964, P < 0.01], while the ratio of residual volume to total lung capacity (RV/TLC) was lower [phenotype A (37 +/- 9)%, phenotype E (44 +/- 10)%, phenotype M (45 +/- 8)%, F = 6.954, P < 0.01]. Patients with different phenotypes showed various levels of IL-6 in exhaled breath condensate [phenotype A (19.9 +/- 6.3) ng/L, phenotype E (16.7 +/- 2.1) ng/L, phenotype M (25.6 +/- 4.4) ng/L, F = 7.749, P < 0.01]. CONCLUSION: Various morphological phenotypes of COPD based on HRCT showed different clinical characteristics and airway inflammation.