Secondary Lung Research Articles

Role of Napsin-A and TTF-1 in differentiating primary from secondary lung carcinoma

Role of Napsin-A and TTF-1 in differentiating primary from secondary lung carcinoma

Engaging At-Risk Rural Residents in Secondary Lung Cancer Prevention.

Rural residents are at elevated risk for lung cancer and related mortality, yet limited research has explored their perspectives on cancer risk or prevention options, including tobacco treatment and lung cancer screening with low-dose computed tomography (LDCT). This qualitative study examined attitudes and beliefs among rural adults who reported either current or former tobacco use, as well as disengagement from the health care system. We conducted 6 focus groups with rural Maine residents at risk for lung cancer based on age and smoking history (n = 50). Semistructured interviews explored participants' knowledge, perceptions, and attitudes regarding lung cancer risk, LDCT screening, and patient provider relationships. Inductive qualitative analysis of interview transcripts was conducted to identify key themes. Participants were cognizant of their elevated lung cancer risk, yet few were aware of LDCT screening. When informed about LDCT, most participants indicated a willingness to undergo screening, although a substantial minority indicated reluctance related to fear and fatalism. Participants generally expressed the belief that relationships with a primary care provider could support their health and identified several provider factors that influence these relationships, including attention and time for patient concerns; respect and non-judgmental, nonstigmatizing attitudes; treating patients as individuals; and provider empathy and emotional support. Rural residents at risk for lung cancer report limited knowledge and substantial ambivalence regarding LDCT screening, but identify provider behaviors that may promote patient-provider relationships and greater engagement with their health. More research is needed to confirm these findings and understand how to help rural residents and healthcare providers work together to reduce lung cancer risk.

Resolvin D2 induces anti-microbial mechanisms in a model of infectious peritonitis and secondary lung infection.

In severe bacterial infections, there is a pro-inflammatory response to promote bacterial clearance but this response can cause tissue injury. Later, the immune system becomes dysregulated and the host is unable to clear a secondary or a pre-existing infection. Specialized Pro-resolving Mediators (SPMs) such as resolvin D2 (RvD2) have been shown to be beneficial for inflammation/infection resolution in animal models of sepsis but in vivo mechanisms by which RvD2 may promote bacterial clearance and/or attenuate deleterious effects of a secondary infection have not been fully established. In this study, we used the 2-hit model of cecal ligation and puncture (CLP) induced infectious peritonitis and secondary lung infection with Pseudomonas aeruginosa to find possible antimicrobial and immunomodulatory mechanisms of RvD2. We show that RvD2 given as late as 48h after CLP surgery reduced blood bacterial load without altering plasma cytokines compared to mice given saline vehicle. RvD2 increased splenic neutrophil accumulation as well as average reactive oxygen species (ROS) production. There was also an increase in an immature leukocyte population the myeloid derived suppressor cells (MDSCs) in the spleen of RvD2 treated mice. RvD2 reduced lung lavage bacterial load 24h after P. aeruginosa administration and significantly decreased lung lavage levels of IL-23, a cytokine essential in the Th-17 inflammatory response. In addition, we show that RvD2 increased the number of non-inflammatory alveolar macrophages after P. aeruginosa administration compared to saline treated mice. The study uncovered an antimicrobial mechanism of RvD2 where RvD2 increases mature neutrophil and MDSC accumulation into the spleen to promote blood bacterial clearance. The study showed that in this 2-hit model, RvD2 promotes lung bacterial clearance, increased non-inflammatory alveolar macrophage number and inhibits an adaptive immune pathway providing evidence of its resolution mechanism in secondary pulmonary infection.

Lactobacillus rhamnosus Restores Antiviral Signaling and Attenuates Cytokines Secretion from Human Bronchial Epithelial Cells Exposed to Cigarette Smoke and Infected with SARS-CoV-2.

Individuals with chronic obstructive pulmonary disease (COPD) are more susceptible to exacerbation crisis triggered by secondary lung infections due to the dysfunction of antiviral signaling, principally via suppression of IFN-γ. Although the probiotic is known for controlling pulmonary inflammation in COPD, the influence of the Lactobacillus rhamnosus (Lr) on antiviral signaling in bronchial epithelium exposed to cigarette smoke extract (CSE) and viruses, remains unknown. Thus, the present study investigated the Lr effect on the antiviral signaling and the secretion of inflammatory mediators from bronchial epithelial cells (16HBE cells) exposed to CSE and SARS-CoV-2. The 16HBE cells were cultured, treated with Lr, stimulated with CSE, and infected with SARS-CoV-2. The cellular viability was evaluated using the MTT assay and cytotoxicity measured by lactate dehydrogenase (LDH) activity. The viral load, TLR2, TLR3, TLR4, TLR7, TLR8, MAVS, MyD88, and TRIF were quantified using specific PCR. The pro-inflammatory mediators were measured by a multiplex biometric immunoassay, and angiotensin converting enzyme 2 (ACE2) activity, NF-κB, RIG-I, MAD5, and IRF3 were measured using specific ELISA kits. Lr decreased viral load, ACE2, pro-inflammatory mediators, TLR2, TLR4, NF-κB, TLR3, TLR7, and TLR8 as well as TRIF and MyD88 expression in CSE and SARS-CoV-2 -exposed 16HBE cells. Otherwise, RIG-I, MAD5, IRF3, IFN-γ, and the MAVS expression were restored in 16HBE cells exposed to CSE and SARS-CoV-2 and treated with Lr. Lr induces antiviral signaling associated to IFN-γ secreting viral sensors and attenuates cytokine storm associated to NF-κB in bronchial epithelial cells, supporting its emerging role in prevention of COPD exacerbation.

Radiotherapy-induced secondary lung cancer: a medical case report

Radiotherapy-induced secondary lung cancer: a medical case report

Evaluation of the efficacy of several sclerosing agents for pleurodesis in rats

Objective: This study aims to evaluate the efficiencies and effects of different sclerosing agents. Materials and Methods: Thirty-five female Wistar-albino rats were included in this study and divided into five groups randomly. Isotonic saline (group 1), iodopovidone (group 2), rifamycin (group 3), autologous blood (group 4), talc (group 5) were given into intrapleural space. On postoperative 28th day, ipsilateral and contralateral pleural and parenchymal fibrosis and inflammation were evaluated. Results: There were statistically differences between control and other groups on macroscopically pleural fibrosis examination (p=0.004, p=0.001, p=0.001, p=0.000, respectively). Microscopically pleural fibrosis were determined in all groups when compared to control group (p=0.023, p=0.023, p=0.035, p=0.001, respectively). There were no significant differences between sclerosing agent groups (p>0.05). Significant differences were observed according to microscopic pleural inflammation evaluation between talc group and other groups. There was superiority in talc group according to intraparenchymal inflammation grade compared to other groups (p=0.010, p=0.042, p=0.030, respectively). Macroscopically, fibrosis and microscopically, inflammation were significantly observed between talc and other groups in the contralateral pleura (p = 0.037and p=0.009, respectively). Conclusion: Iodopovidone, autologous blood, talc, and rifamycin can be used as effective pleurodesis agents. However, we found that rifamycin and autologous blood are safer as effective pleurodesis agents. We think that these two agents can be used in patients with secondary lung diseases due to their less intraparenchymal inflammation rates. It may be advantageous to prefer other sclerosing agents which has lower costs and less side effects comparing to talc.

Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma.

The 8th edition of the TNM stage classification of lung cancer was developed based on an evaluation of the 5-year prognosis using an international database. Since recurrence after 5 years postoperatively is known to develop, the applicability of the stage classification beyond 5 years after treatment needs to be evaluated. Postoperative prognosis and prognostic indicators were analyzed using data for 648 patients of pathological stage IA adenocarcinoma, who underwent complete resection between 2007 and 2012. The median age was 66 years (interquartile range 60-73 years), and the median follow-up duration was 100 months (interquartile range 70-116 months). Overall survival probabilities for pathological stage IA1, IA2, and IA3 patients were 100%, 96.3%, and 91.5% at 5 postoperative years, and 94.2%, 89.8%, and 83.5% at 10 postoperative years, respectively (IA1 vs IA2: p = 0.05; IA2 vs IA3: p = 0.05). Multivariate analysis for overall survival of patients who survived without recurrence for 5 postoperative years revealed that age (hazard ratio 3.21, p = 0.02) was the only factor that was significantly associated with long-term survival. Stage classification (IA1, IA2, or IA3) was not an associated factor. The incidence of secondary primary lung cancer continued to increase, resulting in an estimated probability of 8.6% at 10 postoperative years. For patients who survived without recurrence for 5 postoperative years, age, not stage classification, was associated with survival thereafter. The long-term follow-up strategy does not need to be modified according to the stage classification, and screening for secondary primary lung cancer should be considered.

The therapeutic inhibition of topoisomerase inhibitor and crizotinib combination in EGFR wild and mutant lung cancer cells

Combination therapy can enhance therapeutic effect by activation of multiple downstream pathways. The present study was aimed to investigate a novel strategy to successfully inhibit the EGFR pathway in EGFR wild and mutated types lung cancer by combination method. Topotecan (TPT) and crizotinib (CRI) were used to evaluate the effect on EGFR-wild, primary and secondary mutant non-small cell lung cancer (NSCLC) cell lines (H1299, HCC827 and H1975 cells). The combination group significantly inhibited the lung cancer growth with combination index (CI) < 1, and they synergistically induced the cell apoptosis by disrupting the balance of Bax and Bcl-xL, loss of mitochondrial membrane potential (MMP), and accumulation of reactive oxygen species (ROS). In addition, EGFR downstream signaling pathways including AKT, ERK, JNK, and p38 MAPK were regulated when treated with the combination regimen. Meanwhile, a nano-liposomes co-loaded CRI and TPT was prepared and exhibited strong cytotoxicity to the lung cancer cells especially H1299 and H1975 cells. The animal study confirmed the synergy between TPT and CRI from the results that they remarkable repressed the tumor growth with the inhibition rate of 81.32 %. The nano-liposomes of TPT and CRI achieved an optimal curative effect (71.52 % of inhibition rate) at 2 mg/kg. Moreover, the synergistic mechanism of the combination was consistent with the in vitro cell experiment by regulating EGFR signaling pathways. Collectively, we proposed a preclinical rationale and potential formulation for the use of a combination therapy consisting of the topoisomerase inhibitor TPT and the ALK-TKI CRI for treatment of lung cancers.

Postoperative radiotherapy might be a risk factor for second primary lung cancer: A population-based study.

BackgroundSurgery is the main curative therapeutic strategy for patients with initial primary lung cancer (IPLC). Most international guidelines recommend regular follow-ups after discharge to monitor patients for tumor recurrence and metastasis. As the overall survival (OS) in patients with lung cancer improves, their risk of secondary primary lung cancer (SPLC) increases. Previous studies on such patients lack separate assessment of different survival outcomes and evaluation of high-risk factors for SPLC. Therefore, we aimed to determine the correlation between high-risk factors and causes of death in patients with SPLC, based on the Surveillance, Epidemiology, and End Results (SEER) database.MethodsWe screened the SEER database for patients with IPLC and SPLC from 2004 to 2015 and included only patients who underwent surgery since the IPLC and in whom the cancer was pathologically verified of an International Classification of Diseases grade of 0-3 and to be non-small-cell lung cancer. The standardized incidence ratio (SIR) was calculated between variables and SPLC. Multivariable Cox proportional-hazards regression analyses were conducted to calculate the correlation of different variables with overall survival (OS) and cancer-specific survival (CSS). A competing-risk model was conducted for SPLC. The effect of baseline bias on survival outcomes by performing propensity score matching analysis in a 1: 6 ratio (SPLC: IPLC).ResultsFor patients aged 0-49 years, the overall SIR was higher in older patients, reaching a maximum of 27.74 in those aged 40-49 years, and at 11.63 in patients aged 50-59 years. The overall SIR was higher for patients who were more recently diagnosed with IPLC and increased with time after diagnosis. Male sex, SPLC (hazard ratio, 1.6173; 95% confidence interval, 1.5505-1.6869; P < 0.001), cancer grade III or IV, lower lobe of the lung, advanced stage and postoperative radiotherapy (PORT) were independently detrimental to OS. In terms of CSS, PORT was a high-risk factor.ConclusionsPostoperative radiotherapy is a risk factor for second primary lung cancer and detrimental to overall and cancer-specific survival in patients who had initial primary lung cancer. These data support the need for life-long follow-up of patients who undergo treatment for IPLC to screen for SPLC.

Protective role of Decylubiquinone against secondary melanoma at lung in B16F10 induced mice by reducing E-cadherin expression and ameliorating ROCKII-Limk1/2-Cofiliin mediated metastasis

Melanoma is one of the most consequential skin cancer with a rising death incidences. Silent but belligerent nature of metastatic sprouting is the leading cause of melanoma related mortality. Invasion of metastatic cells and re-expression of E-Cadherin play the crucial role in the establishment of secondary tumor at distal sites. Thus, manipulation of tumor cell invasion in parallel to regulation of E-Cadherin expression can be considered as potential anti-metastatic strategy. Evidences suggested key role of reactive oxygen species associated ROCK activities in the modulation of metastatic invasion via F-actin stabilization. Here, we first-time report Decylubiquinone, a dietary Coenzyme Q10 analog, as an effective attenuator of pulmonary metastatic melanoma in C57BL/6 mice. Current study depicted detailed molecular interplay associated with Decylubiquinone mediated phosphorylation of ROCKII at Tyr722 along with reduced phosphorylation of ROCKII Ser1366 leading to suppression of Limk1/2-Cofilin-F-actin stabilization axis that finally restricted B16F10 melanoma cell invasion at metastatic site. Analysis further deciphered the role of HNF4α as its nuclear translocation modulated E-Cadherin expression, the effect of reactive oxygen species dependent ROCKII activity in secondarily colonized B16F10 melanoma cells at lungs. Thus unbosoming of related signal orchestra represented Decylubiquinone as a potential remedial agent against secondary lung melanoma.

REACTIVATION MILIARY TB IN THE SETTING OF POSTINFECTIOUS COVID-19 LUNGS

REACTIVATION MILIARY TB IN THE SETTING OF POSTINFECTIOUS COVID-19 LUNGS

608 Anti-CD20 permits secondary lung gene transfer: implications for gene editing approaches in cystic fibrosis

608 Anti-CD20 permits secondary lung gene transfer: implications for gene editing approaches in cystic fibrosis

Radiothérapie en condition stéréotaxique (RTS) pulmonaire : indications dans les stades localisés et aspects post thérapeutiques

Stereotactic ablative radiotherapy is the standard treatment for patients with stage I non-small cell lung cancer who are unfit for surgery or refuse surgery. Surveillance imaging is to assess treatment response and pulmonary toxicity, detect local recurrence and secondary lung cancer. The early detection of recurrence is important for patients for whom a salvage therapy is available. However, changes in lung density on computed tomography are common after stereotactic ablative radiotherapy and can confound the early detection of recurrence.1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Role of 18F-FDG PET/CT in the postoperative follow-up in patients with stage I-III NSCLC: A retrospective single-institution study

BackgroundThe optimal surveillance strategy in patients with resected non-small cell lung cancer (NSCLC) is unknown. Early detection of recurrences by follow-up imaging might improve survival and whole-body 18F-FDG-PET/CT might be the optimal imaging modality given its high accuracy in preoperative staging. Material and methodsData from a single-center cohort of 205 patients with resected stage I-III NSCLC and FDG-PET/CT surveillance was retrospectively collected. Patients had preoperative FDG-positive tumors and FDG-PET/CT at 6, 12, 24 months, chest CT at 18 months. Thereafter, annual chest CT was performed for stage I-II, annual FDG-PET/CT for stage III. ResultsWith a median follow-up of 26.3 months (range, 4.1–60.6), the rate for recurrence and secondary primary lung cancer (SPLC) was 22 % and 8 %, respectively. Associated symptoms were present in 48 % (recurrence) and 18 % (SPLC) of patients. Overall, 83 % of recurrences, and 65 % of SPLC were detected on FDG-PET/CT. 82 % of recurrences were detected in one of the first two follow-up PET/CT scans. Second curatively intended treatment (SCIT) was possible in 37 % of patients with recurrence and 100 % with SPLC. The 2-year recurrence-free survival rate after SCIT for recurrence was 53 % [95 %CI; 31–91 %]. Non-malignant FDG-positive findings occurred in 25 % of patients (71 % possible infections). ConclusionIn our cohort of patients, more than 80% of all recurrences were identified in one of the three FDG-PET/CTs performed as part of our imaging protocol during the first two years after resection. Nearly all patients with non-distant recurrence qualified for a SCIT. Further studies are needed to identify patients who might benefit from an even more intensive surveillance strategy.

1638P Risk and prognosis of secondary lung cancer after radiation therapy for thoracic malignancies

Radiation therapy (RT) is a crucial modality for the local control of thoracic cancer (TC), but the effect of pelvic RT on the development of secondary malignancy is still unclear. The aim of this study was to determine the association between exposure to radiotherapy for the treatment of TC and subsequent secondary lung cancer (SLC). The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for the thoracic cancer. Multiple Cox regression analyses and Fine&Gray competing risk regression were employed to assess the cumulative incidence of SLC. Poisson regression and multiple primary standardized incidence ratios (SIR) were used to evaluate the radiotherapy-associated risk for patients receiving RT. Subgroup analyses of patients stratified by latency time since TC diagnosis, age at TC diagnosis, and calendar year of TC diagnosis stage were also performed. Overall survival and secondary lung cancer -related death were compared among the RT and no radiation therapy (NRT) groups by using Kaplan-Meier analysis and competitive risk analysis. A total of 329,129 observations, 147,847 of whom had been treated with RT, and 6,799 patients developed SLC. Receiving radiotherapy was related to a higher risk of developing SLC for TC patients in multiple Cox regression analyses (adjusted HR, 1.25; 95% CI, 1.19-1.32; P<0.001). The cumulative incidence of developing SLC in TC patients with RT (3.8%) was higher than the cumulative incidence (2.9%) in TC patients with NRT (P=0.012). The results of the dynamic SIR and Poisson regression analysis for SLC revealed that a slightly increased risk of SLC was observed after RT in the late-stage latency and was significantly associated to the variations of age at TC diagnosis. The 10-year OS among SLC patients after RT were comparable to SLC patients after NRT in different site of TC. Radiotherapy for thoracic cancer was associated with higher risks of developing secondary lung cancer compared with patients unexposed to radiotherapy.

Spiral CT Image Characteristics and Differential Diagnosis Secondary Pulmonary Tuberculosis and Lung Cancer Based on Visual Sensors.

Helical CT plain scan has high spatial and area resolution, which is beneficial to the extraction of CT features of pulmonary nodules, and is of great significance for the diagnosis and differential diagnosis of pulmonary diseases. In order to deeply study the role of visual sensor image algorithm in CT image, this paper adopts clinical simulation method, data fusion method, and image acquisition method to collect images, analyze CT image features, and simplify the algorithm and create a CT model that can better diagnose secondary tuberculosis and lung cancer. We selected 45 patients with lung disease in this group, with an average age of 38 years. At the same time, the consistency analysis results of the diameter and plain CT value data of the five groups of cases measured by two observers are between 0.82 and 0.88, which has a good consistency. We could find that the nodule diameters of the five groups of cases were different (F =16.99, P < 0.01), and the difference was statistically significant (P < 0.06), indicating that our data are not only accurate but also very reliable. ROC was used to analyze the precise value of CT values in the pulmonary tuberculosis group and lung cancer group, intrapulmonary lymph node group, and pulmonary hamartoma group to determine the cutoff value. The results showed that the AUC values of the pulmonary tuberculosis group and the lung cancer group were 0.788, and the middle was the largest, indicating that the values were guaranteed. The basic realization starts with visual sensor technology and designs a clinical model that can more accurately identify CT images and differential diagnosis.

Dual effects of supplemental oxygen on pulmonary infection, inflammatory lung injury, and neuromodulation in aging and COVID-19.

Clinical studies have shown a significant positive correlation between age and the likelihood of being infected with SARS-CoV-2. This increased susceptibility is positively correlated with chronic inflammation and compromised neurocognitive functions. Postmortem analyses suggest that acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), with systemic and lung hyperinflammation, can cause significant morbidity and mortality in COVID-19 patients. Supraphysiological supplemental oxygen, also known as hyperoxia, is commonly used to treat decreased blood oxygen saturation in COVID-19 patients. However, prolonged exposure to hyperoxia alone can cause oxygen toxicity, due to an excessive increase in the levels of reactive oxygen species (ROS), which can overwhelm the cellular antioxidant capacity. Subsequently, this causes oxidative cellular damage and increased levels of aging biomarkers, such as telomere shortening and inflammaging. The oxidative stress in the lungs and brain can compromise innate immunity, resulting in an increased susceptibility to secondary lung infections, impaired neurocognitive functions, and dysregulated hyperinflammation, which can lead to ALI/ARDS, and even death. Studies indicate that lung inflammation is regulated by the central nervous system, notably, the cholinergic anti-inflammatory pathway (CAIP), which is innervated by the vagus nerve and α7 nicotinic acetylcholine receptors (α7nAChRs) on lung cells, particularly lung macrophages. The activation of α7nAChRs attenuates oxygen toxicity in the lungs and improves clinical outcomes by restoring hyperoxia-compromised innate immunity. Mechanistically, α7nAChR agonist (e.g., GAT 107 and GTS-21) can regulate redox signaling by 1) activating Nrf2, a master regulator of the antioxidant response and a cytoprotective defense system, which can decrease cellular damage caused by ROS and 2) inhibiting the activation of the NF-κB-mediated inflammatory response. Notably, GTS-21 has been shown to be safe and it improves neurocognitive functions in humans. Therefore, targeting the α7nAChR may represent a viable therapeutic approach for attenuating dysregulated hyperinflammation-mediated ARDS and sepsis in COVID-19 patients receiving prolonged oxygen therapy.

Study on combination therapy for lung cancer through pemetrexed-loaded mesoporous polydopamine nanoparticles.

Lung cancer is one of the most commonly diagnosed cancers, and surgical resection is the optimal choice for the primary lung tumor. But for the secondary lung cancer, chemotherapy and combined radiotherapy still are the main strategies. To realize the combined treatment for non-small cell lung cancer (NSCLC), in this work, a nanoplatform based on pemetrexed (PE)-loaded mesoporous polydopamine (MPDA) nanoparticles were investigated. PE, a special therapeutic drug for NSCLC, was loaded into the MPDA nanoparticles via electrostatic attraction and was encapsulated with polyvinyl pyrrolidone (PVP). The results showed that, when irradiating with 808 nm near-infrared light, the PE loaded MPDA (MPDA@PE@PVP) nanoparticles have excellent photothermal conversion properties, which would result in increase of ambient temperature and could accelerate the release of PE. In vitro cell experiments proved that MPDA@PE@PVP nanoparticles have excellent killing ability for NSCLC A549 cells by the functions of PE and photothermal ability of MPDA nanoparticles. Meanwhile, the intra-cellular reactive oxygen species (ROS) levels of A549 cells in the MPDA@PE@PVP nanoparticle-treated group could be promoted significantly after irradiation, leading to the death of A549 cells. In vivo animal model results showed that MPDA@PE@PVP nanoparticles could gather at the tumor site by enhanced permeability and retention (EPR) effect and have significant inhibition ability for lung tumor by synergistic therapy of chemotherapy, photothermal therapy and photodynamic therapy.

Predictors of Secondary Lung Cancer Among Hodgkin Lymphoma Survivors: A Nationwide Analysis

PurposeThere is insufficient data regarding the incidence rate of secondary lung cancer among Hodgkin lymphoma (HL) survivors and the predisposing factors. MethodsWe analyzed the data from the cohort of patients who had HL between 1973 and 2015 using the Surveillance Epidemiology and End Results database (SEER). Data on patient's age, gender, year of diagnosis with HL, Ann-Arbor stage, Histology, racial groups, date of last follow-up, date of death, and treatment modalities were collected. ResultsWe identified a total of 56,856 patients with HL; of those, 862 had secondary lung cancer, with an incidence rate of 157 (95%CI: 147-168) per 100,000 person-years. The median overall survival from time of HL diagnosis for those with secondary lung cancer was 12.1 years (95% CI: 10.7-13) compared to 27.1 years (95% CI: 26.5-27.6) for those who did not develop lung cancer (log-rank P-value of <.01). After propensity score weighting, radiation therapy was associated with a higher risk of secondary lung cancer (hazard ratio (HR): 1.23, 95% CI: 1.002-1.55) with a P-value of 0.048. Older age at the time of HL diagnosis and male gender were associated with higher risk, with an HR of 1.07 (95% CI 1.062-1.073) and an HR of 1.602 (95% CI 1.33-1.94), respectively. Furthermore, chemotherapy increased the risk only among older age groups. ConclusionOlder age at the time of HL diagnosis, male gender, radiation therapy, and chemotherapy only among older age groups were associated with higher risk for secondary lung cancer, with 50% of the cases occurring within 9.1 years following HL diagnosis.

Increased Heme Oxygenase 1 Expression upon a Primary Exposure to the Respiratory Syncytial Virus and a Secondary Mycobacterium bovis Infection.

The human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in infants. Because recurrent epidemics based on reinfection occur in children and adults, hRSV has gained interest as a potential primary pathogen favoring secondary opportunistic infections. Several infection models have shown different mechanisms by which hRSV promotes immunopathology to prevent the development of adaptive protective immunity. However, little is known about the long-lasting effects of viral infection on pulmonary immune surveillance mechanisms. As a first approach, here we evaluated whether a primary infection by hRSV, once resolved, dampens the host immune response to a secondary infection with an attenuated strain of Mycobacterium bovis (M. Bovis) strain referred as to Bacillus Calmette-Guerin (BCG). We analyzed leukocyte dynamics and immunomodulatory molecules in the lungs after eleven- and twenty-one-days post-infection with Mycobacterium, using previous hRSV infected mice, by flow cytometry and the expression of critical genes involved in the immune response by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Among the latter, we analyzed the expression of Heme Oxygenase (HO)-1 in an immunization scheme in mice. Our data suggest that a pre-infection with hRSV has a conditioning effect promoting lung pathology during a subsequent mycobacterial challenge, characterized by increased infiltration of innate immune cells, including interstitial and alveolar macrophages. Our data also suggest that hRSV impairs pulmonary immune responses, promoting secondary mycobacterial colonization and lung survival, which could be associated with an increase in the expression of HO-1. Additionally, BCG is a commonly used vaccine that can be used as a platform for the generation of new recombinant vaccines, such as a recombinant BCG strain expressing the nucleoprotein of hRSV (rBCG-N-hRSV). Therefore, we evaluated if the immunization with rBCG-N-hRSV could modulate the expression of HO-1. We found a differential expression pattern for HO-1, where a higher induction of HO-1 was detected on epithelial cells compared to dendritic cells during late infection times. This is the first study to demonstrate that infection with hRSV produces damage in the lung epithelium, promoting subsequent mycobacterial colonization, characterized by an increase in the neutrophils and alveolar macrophages recruitment. Moreover, we determined that immunization with rBCG-N-hRSV modulates differentially the expression of HO-1 on immune and epithelial cells, which could be involved in the repair of pulmonary tissue.