Dipeptidase-1 Is an Adhesion Receptor for Neutrophil Recruitment in Lungs and Liver.

A hallmark feature of inflammation is the orchestrated recruitment of neutrophils from the bloodstream into inflamed tissue. Although selectins and integrins mediate recruitment in many tissues, they have a minimal role in the lungs and liver. Exploiting an unbiased in vivo functional screen, we identified a lung and liver homing peptide that functionally abrogates neutrophil recruitment to these organs. Using biochemical, genetic, and confocal intravital imaging approaches, we identified dipeptidase-1 (DPEP1) as the target and established its role as a physical adhesion receptor for neutrophil sequestration independent of its enzymatic activity. Importantly, genetic ablation or functional peptide blocking of DPEP1 significantly reduced neutrophil recruitment to the lungs and liver and provided improved survival in models of endotoxemia. Our data establish DPEP1 as a major adhesion receptor on the lung and liver endothelium and identify a therapeutic target for neutrophil-driven inflammatory diseases of the lungs.

Sexual Health Assessment in Women with Lung Cancer study: Sexual health assessment in women with lung cancer.

BACKGROUND: Sexual health is understudied and underreported in patients with lung cancer, and most data precede the approval of widely used targeted therapies and immune checkpoint inhibitors. The authors sought to evaluate the prevalence of sexual dysfunction in women with lung cancer in our current clinical environment. METHODS: This cross-sectional survey study was administered online to 249 women via the GO2 for Lung Cancer (GO2) Registry, using the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Measures questionnaire. Participants were recruited between June 2020 to June 2021. Eligibility criteria included age >18 years, self-identifying as a woman, fluency in English, and a lung cancer diagnosis within 10 years. RESULTS: Most (67%) had stage IV lung cancer and 47% were receiving targeted therapy; 66% were undergoing active treatment. Despite 54% of participants reporting "recent" sexual activity, most (77%) indicated having little to no interest in sexual activity and 48% reported recent minimal satisfaction with their sex life. The most common reasons negatively affecting participants' satisfaction with their sex life included fatigue (40%) and feeling sad/unhappy (28%). Common reasons for lack of recent sexual activity included lack of interest (68%) and vaginal dryness or pain (30%). Compared to pre-diagnosis, women were significantly less likely to have recent interest in sexual activity. In multivariable logistic-regression, vaginal dryness showed a significant negative association with recent interest in sexual activity. CONCLUSIONS: Sexual dysfunction is prevalent in women with lung cancer. Sexual health should be integrated into routine care for patients with lung cancer.

Leveraging social media to increase lung cancer screening awareness, knowledge and uptake among high-risk populations (The INSPIRE-Lung Study): study protocol of design and methods of a community-based randomized controlled trial.

BACKGROUND: Lung cancer is the leading cause of cancer death for both men and women in the United States. The National Lung Screening Trial (NLST) demonstrated that low-dose computed tomography (LDCT) screening can reduce lung cancer mortality among high-risk individuals, but uptake of lung screening remains low. Social media platforms have the potential to reach a large number of people, including those who are at high risk for lung cancer but who may not be aware of or have access to lung screening. METHODS: This paper discusses the protocol for a randomized controlled trial (RCT) that leverages FBTA to reach screening-eligible individuals in the community at large and intervene with a public-facing, tailored health communication intervention (LungTalk) to increase awareness of, and knowledge about, lung screening. DISCUSSION: This study will provide important information to inform the ability to refine implementation processes for national population efforts to scale a public-facing health communication focused intervention using social media to increase screening uptake of appropriate, high-risk individuals. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (#NCT05824273).

An examination of two dichotomies: Women with lung cancer and living with lung cancer as a chronic disease.

Lung cancer remains the leading cause of cancer death globally, yet with many recent advances in the diagnosis and treatment of lung cancer, the face of the disease is shifting. Historically, lung cancer is often thought of as a predominantly male disease with more than twice as many men as women being diagnosed worldwide-mostly due to the influence of smoking as the leading risk factor. However, lung cancer is also the second leading cause of cancer death in women and there is a growing population of young women who have never smoked and are being diagnosed. The past decade has seen groundbreaking innovations in both the early detection and treatment of lung cancer. In this new era, survival rates are beginning to increase and many of those diagnosed are finding themselves in a new situation-living long term with a deadly cancer. Here, we review pertinent aspects of women and lung cancer as well as the concept of living with lung cancer as a chronic disease to give a new perspective on the changing face of lung cancer treatment and care.

Survivor guilt: The secret burden of lung cancer survivorship.

Objectives: Historically, long-term survival following diagnosis of lung cancer has been a rare occurrence. An overall poor prognosis and the low likelihood of long-term survival are thought to precipitate survivors experiencing what is referred to as survivor guilt. This study explored the prevalence and nature of survivor guilt among lung cancer survivors. Methods: Lung cancer survivors (n = 108) completed an online survey through a national organization's online community platform. This survey included a commonly used measure of survivor guilt targeting lung cancer and a single item that asked about whether they had experienced survivor guilt associated with lung cancer. Additionally, survivors were asked to provide open-ended descriptions of survivor guilt. In-depth thematic analysis was used to analyze these in-depth responses from those with the highest guilt scores on the survey measure (top quartile). Results: Survey responses revealed a majority of study respondents endorsed survivor guilt with 55% reporting an experience of survivor guilt associated with lung cancer. In addition, 63.9% of respondents scored above the mean on the survivor guilt scale. Qualitative analysis revealed five recurring themes among respondents with the highest survivor guilt scores (top quartile): 1) mentioning the death of others, 2) questioning "why not me?" 3) the role of the passage of time on emotions experienced, 4) the role of demographic and clinical characteristics' on survivor guilt, and 5) strategies for coping with survivor guilt. Conclusions: This study identifies survivor guilt in lung cancer survivors and raises clinical awareness that managing survivor guilt is a psychosocial challenge for lung cancer survivors. Results highlight the need for addressing this critical issue.

Far Upstream Element-Binding Protein 1 Binds the 3' Untranslated Region of PKD2 and Suppresses Its Translation.

Autosomal dominant polycystic kidney disease pathogenesis can be recapitulated in animal models by gene mutations in or dosage alterations of polycystic kidney disease 1 (PKD1) or PKD2, demonstrating that too much and too little PKD1/PKD2 are both pathogenic. Gene dosage manipulation has become an appealing approach by which to compensate for loss or gain of gene function, but the mechanisms controlling PKD2 expression remain incompletely characterized. In this study, using cultured mammalian cells and dual-luciferase assays, we found that the 3' untranslated region (3'UTR) of PKD2 mRNA inhibits luciferase protein expression. We then identified nucleotides 691-1044, which we called 3FI, as the 3'UTR fragment necessary for repressing the expression of luciferase or PKD2 in this system. Using a pull-down assay and mass spectrometry we identified far upstream element-binding protein 1 (FUBP1) as a 3FI-binding protein. In vitro overexpression of FUBP1 inhibited the expression of PKD2 protein but not mRNA. In embryonic zebrafish, FUBP1 knockdown (KD) by morpholino injection increased PKD2 expression and alleviated fish tail curling caused by morpholino-mediated KD of PKD2. Conversely, FUBP1 overexpression by mRNA injection significantly increased pronephric cyst occurrence and tail curling in zebrafish embryos. Furthermore, FUBP1 binds directly to eukaryotic translation initiation factor 4E-binding protein 1, indicating a link to the translation initiation complex. These results show that FUBP1 binds 3FI in the PKD2 3'UTR to inhibit PKD2 translation, regulating zebrafish disease phenotypes associated with PKD2 KD.

Stigma, self-blame, and satisfaction with care among patients with lung cancer.

OBJECTIVE: We sought to understand the experiences of patients with lung cancer and to see if attitudes varied by demographic factors. METHODS: We administered a 63-question survey by phone or online among 174 patients with lung cancer. Factor analysis was used to identify two groups of questions with a conceptual relationship and high Cronbach's alphas, stigma and satisfaction with care. We used a multivariable analysis to identify predictors of self-blame and the factors of stigma and satisfaction with care. RESULTS: Patients were satisfied with the quality of their care and treatment choices but did not feel that there is enough public support for or research in lung cancer. Predictors of lower satisfaction with care were never being a smoker, lack of college education, not living in a rural location, refusing to report income, and not knowing/not being sure of stage. Self-blame was modest; in multivariable analysis, predictors of self-blame were believing that smoking was a cause of their lung cancer, younger age, male sex, living in a suburban location, and not knowing/not being sure of the stage of the cancer. Reported stigma was low and the only predictor for stigma was being married. Despite low scores on their personal experience of stigma, patients reported a high degree of stigmatization of lung cancer in general. Smoking was a significant predictor of personal stigma. CONCLUSION: Despite satisfaction with their treatment and care, lung cancer patients feel that society stigmatizes them as a general population. Patients who smoke are more likely to report that they have personally experienced stigma.

Real-world analysis of the relationships between smoking, lung cancer stigma, and emotional functioning.

INTRODUCTION: People diagnosed with lung cancer experience high rates of distress, which can be compounded by the stigma of the disease. This study assessed a real-world population to understand patient-reported emotional functioning, types of stigma experienced, and relationship with smoking history. METHODS: Questionnaires using validated survey tools assessing demographics, smoking history, stigma, and quality of life (EORTC QLQ-C30 Emotional Functioning Scale) were analyzed from 539 global participants in the Lung Cancer Registry between November 2019 and July 2022. The associations between smoking history and self-reported internalized and perceived stigma and constrained disclosure of lung cancer diagnosis, as well as the potential impact of stigma on emotional functioning, were examined using multivariable logistic regression models. RESULTS: Among the broad geographic mix of study participants, all types of lung cancer stigma were associated with decreased emotional functioning due to a combination of factors including depression, anxiety, stress, and irritability. Participants who reported a history of current or former smoking experienced higher levels of internalized stigma and perceived stigma. Constrained disclosure about a diagnosis was common, associated with decreased emotional functioning, and not related to a history of smoking. Smoking status itself was not associated with reduced emotional functioning, implicating the role of stigma in distress. CONCLUSIONS: In this study, all types of lung cancer stigma were associated with clinically important decreases in emotional functioning. This impact was not dependent on smoking history. Internalized and perceived stigma were associated with the presence of a smoking history. These findings have implications for proper psychosocial care of people diagnosed with lung cancer.

Influences on Lung Cancer Screening Initiation and Retention in Rural Alabama.

INTRODUCTION/OBJECTIVES: Despite the introduction of lung cancer screening using low dose computed tomography (LDCT), overall screening rates in the U.S. remain low, with certain populations including Black and rural communities experiencing additional disparities. The primary objective of this study was to understand the facilitators of lung cancer screening initiation and retention in Alabama reported by people at risk from mostly rural, mostly Black populations in Jefferson County-including the urban center of Birmingham-and 6 rural counties: Choctaw, Dallas, Greene, Hale, Marengo, and Sumter. METHODS: We conducted semi-structured telephone interviews with 58 people who underwent lung cancer screening between December 2019 and January 2022. Participant responses were recorded by the interviewer for analysis. Open-ended responses were coded to identify emergent themes. RESULTS: The most reported influences to initiate screening were information or suggestion from a Community Health Advisor (CHAs) or the supervising county coordinator, suggestion from a friend, or consideration of a personal history of smoking. Most participants reported multiple influences. Physicians were not very influential in decisions to initiate screening, but they were extremely influential in participants' intent to continue screening, both positively and negatively. Knowing the recommended timeline for their annual scans was also a predictor of intention to continue screening. Participants screened during the COVID-19 state of emergency expressed less certainty about dates of next scans and more ambivalence about intention to continue screening. CONCLUSIONS: This study shows the benefit of using multiple methods to support increased awareness of and interest in lung cancer screening, particularly when educational messaging through CHAs is used. Clear guideline-based messages from healthcare providers about recommended screening is important for increasing retention. COVID-19 related implementation challenges impacted screening recruitment and retention. Future research is warranted to further explore use of CHAs in lung cancer screening.

Health inequities across the lung cancer care continuum in ten marginalized populations: a narrative review.

Background and Objective: Lung cancer remains the deadliest cancer in the United States. Although lung cancer screening and innovative treatment options are available, accessing these interventions remains a barrier for marginalized communities due to social and structural challenges that influence health care access, which has led to worse outcomes when compared to Non-Hispanic Whites (NHW) and non-marginalized populations. The objective of this study is to examine disparities in lung cancer and social/structural factors within ten critical populations (racial/ethnic minorities, low income, rural, LGBTQIA+, women, veteran and active duty, and small cell lung cancer) across the continuum of lung cancer care. Methods: Five databases (PubMed, the Cochrane Library, EMBASE, Web of Knowledge, and EBSCO Discovery Service) were queried from February 2022-June 2022. The inclusion criteria were (I) peer-reviewed academic journals published in English between the years 2000 and 2022; (II) research that focused on disparities across the lung cancer continuum; and (III) research articles addressing social and structural barriers to lung cancer health care access. A total of 95 articles and 24 reports were used for this narrative review. Key Content and Findings: Across the ten populations, consistent disparities were observed in lung cancer screening and treatment, exhibited by lower uptake in screening, treatment, clinical trials, and biomarker testing. Significant themes contributing to these disparities were socioeconomic status, transportation, language, historic trauma, provider bias or lack of cultural training, and lack of health care access, in part due to insurance coverage. Conclusions: Future studies are needed to further develop meaningful solutions to disparities in health outcomes and access for those who are at risk, diagnosed with, or surviving lung cancer from marginalized populations.

Leveraging social media to increase lung cancer screening awareness, knowledge and uptake among high-risk populations (The INSPIRE-Lung Study): Study protocol of design and methods of a community-based randomized controlled trial.

Background. Lung cancer is the leading cause of cancer death for both men and women in the United States. The National Lung Screening Trial (NLST) demonstrated that low-dose computed tomography (LDCT) screening can reduce lung cancer mortality among high-risk individuals, but uptake of lung screening remains low. Social media platforms have the potential to reach a large number of people, including those who are at high risk for lung cancer but who may not be aware of or have access to lung screening. Methods. This paper discusses the protocol for a randomized controlled trial (RCT) that leverages FBTA to reach screening-eligible individuals in the community at large and intervene with a public-facing, tailored health communication intervention ( LungTalk ) to increase awareness of, and knowledge about, lung screening. Discussion. This study will provide important information to inform the ability to refine implementation processes for national population efforts to scale a public-facing health communication focused intervention using social media to increase screening uptake of appropriate, high-risk individuals. Trial Registration : The trial is registered at clinicaltrials.gov (#NCT05824273).

Patient-reported impact of symptoms in lung cancer (PRISM-LC).

Background: Individuals with lung cancer (LC) face a variety of symptoms that significantly impact their lives. We use extensive patient input to determine the relative importance and prevalence of these symptoms and identify which demographic features are associated with a higher level of disease burden. Methods: We performed semi-structured qualitative interviews with participants with LC to identify potentially important symptoms. We then conducted a cross-sectional study, in which participants rated the relative importance of 162 individual symptoms covering 14 symptomatic themes. Participant responses were analyzed by age, sex, disability status, disease duration, LC stage, type of treatment received, and smoking history, among other categories. Results: Our cross-sectional study had 139 participants with LC. The most prevalent symptomatic themes reported by this population were fatigue (85.5%), impaired sleep and daytime sleepiness (73.5%), and emotional issues (73.0%). The symptomatic themes that had the greatest average impact (on a scale of 0 to 4, with 4 being the most impactful) were social role dissatisfaction (1.67), inability to do activities (1.64), and fatigue (1.60). Disability status had the strongest association with symptomatic theme prevalence. LC stage (stage IV), receipt of therapy, and smoking experience were also associated with higher frequency of symptomatic themes. Conclusions: Individuals with LC face diverse and disease-specific symptoms that affect their daily lives. Patient insight on the prevalence and relative importance of these symptoms is invaluable to advance meaningful therapeutic interventions.

Getting ready for prime time: Recommended adaptations of an Empathic Communication Skills training intervention to reduce lung cancer stigma for a national multi-center trial.

Building upon prior work developing and pilot testing a provider-focused Empathic Communication Skills (ECS) training intervention, this study sought feedback from key invested partners who work with individuals with lung cancer (i.e. stakeholders including scientific and clinical advisors and patient advocates) on the ECS training intervention. The findings will be used to launch a national virtually-delivered multi-center clinical trial that will examine the effectiveness and implementation of the evidence-based ECS training intervention to reduce patients' experience of lung cancer stigma. A 1-day, hybrid, key invested partners meeting was held in New York City in Fall 2021. We presented the ECS training intervention to all conference attendees (N = 25) to seek constructive feedback on modifications of the training content and platform for intervention delivery to maximize its impact. After participating in the immersive training, all participants engaged in a group discussion guided by semi-structured probes. A deductive thematic content analysis was conducted to code focus group responses into 12 distinct a priori content modification recommendations. Content refinement was suggested in 8 of the 12 content modification themes: tailoring/tweaking/refining, adding elements, removing elements, shortening/condensing content, lengthening/extending content, substituting elements, re-ordering elements, and repeating elements. Engagement and feedback from key invested multi-sector partner is a valuable resource for intervention content modifications. Using a structured format for refining evidence-based interventions can facilitate efforts to understand the nature of modifications required for scaling up interventions and the impact of these modifications on outcomes of interest. ClinicalTrials.gov Identifier: NCT05456841.

This study was done to get feedback from people who are involved with patients with lung cancer (PwLCs) including scientists, clinicians, and patient advocates on training in Empathic Communication Skills (ECS). The training is intended to reduce PwLCs experience of lung cancer stigma. The feedback is being used to help prepare for launching the training program in multiple cancer centers across the USA to test how well the training will work to reduce the stigma felt by PwLCs. A one-day, hybrid (in-person and virtual attendees) meeting was held in New York City in October 2021. We presented the original version of the ECS training program to all conference attendees (N = 25) to get feedback on modifications to improve the training program for the larger study planned at many cancer centers. After the training, all meeting attendees participated in a semi-structured group discussion. The content of the discussion was analyzed and sorted into 12 distinct categories that were defined before the meeting. Changes to the content were suggested in 8 of the 12 categories. These changes included tailoring/tweaking/refining, adding elements, removing elements, shortening/condensing content, lengthening/extending content, substituting elements, re-ordering elements, and repeating elements. Engaging and getting feedback from people involved in a topic is a good way to improve content and delivery of training materials.

Longitudinal nucleocapsid antibody testing reveals undocumented SARS-CoV-2 infections in patients with lung cancer.

Patients diagnosed with lung cancer (LC) exhibit increased susceptibility to SARS-CoV-2 infection. Rodilla et al. monitor the levels of plasma anti-nucleocapsid antibodies within a cohort of fully vaccinated LC patients and reveal that the actual infection rate is nearly twice the documented rate, indicating a significant prevalence of unreported cases.

Adaptor protein 1 complexes regulate intracellular trafficking of the kidney anion exchanger 1 in epithelial cells.

Distal renal tubular acidosis (dRTA) can be caused by mutations in the gene encoding the anion exchanger 1 (AE1) and is characterized by defective urinary acidification, metabolic acidosis, and renal stones. AE1 is expressed at the basolateral membrane of type A intercalated cells in the renal cortical collecting duct (kAE1). Two dRTA mutations result in the carboxyl-terminal truncation of kAE1; in one case, the protein trafficked in a nonpolarized way in epithelial cells. A recent yeast two-hybrid assay showed that the carboxyl-terminal cytosolic domain of AE1 interacts with adaptor protein complex 1 (AP-1A) subunit µ1A (mu-1A; Sawasdee N, Junking M, Ngaojanlar P, Sukomon N, Ungsupravate D, Limjindaporn T, Akkarapatumwong V, Noisakran S, Yenchitsomanus PT. Biochem Biophys Res Commun 401: 85-91, 2010). Here, we show the interaction between kAE1 and mu-1A and B in vitro by reciprocal coimmunoprecipitation in epithelial cells and in vivo by coimmunoprecipitation from mouse kidney extract. When endogenous mu-1A (and to a lesser extent mu-1B) was reduced, kAE1 protein was unable to traffic to the plasma membrane and was rapidly degraded via a lysosomal pathway. Expression of either small interfering RNA-resistant mu-1A or mu-1B stabilized kAE1 in these cells. We also show that newly synthesized kAE1 does not traffic through recycling endosomes to the plasma membrane, suggesting that AP-1B, located in recycling endosomes, is not primarily involved in trafficking of newly synthesized kAE1 when AP-1A is present in the cells. Our data demonstrate that AP-1A regulates processing of the basolateral, polytopic membrane protein kAE1 to the cell surface and that both AP-1A and B adaptor complexes are required for normal kAE1 trafficking.

Benefits and Limitations of Virtual Recruitment: Perspectives From Subspeciality Directors.

BACKGROUND AND OBJECTIVES: Because of the coronavirus disease 2019 pandemic and recommendations from a range of leaders and organizations, the pediatrics subspecialty 2020 recruitment season was entirely virtual. Minimal data exist on the effect of this change to guide future strategies. The aim of this study was to understand the effects of virtual recruitment on pediatric subspecialty programs as perceived by program leaders. METHODS: This concurrent, triangulation, mixed-methods study used a survey that was developed through an iterative (3 cycles), consensus-building, modified Delphi process and sent to all pediatric subspecialty program directors (PSPDs) between April and May 2021. Descriptive statistics and thematic analysis were used, and a conceptual framework was developed. RESULTS: Forty-two percent (352 of 840) of PSPDs responded from 16 of the 17 pediatric (94%) subspecialties; 60% felt the virtual interview process was beneficial to their training program. A majority of respondents (72%) reported cost savings were a benefit; additional benefits included greater efficiency of time, more applicants per day, greater faculty involvement, and perceived less time away from residency for applicants. PSPDs reported a more diverse applicant pool. Without an in-person component, PSPDs worried about programs and applicants missing informative, in-person interactions and applicants missing hospital tours and visiting the city. A model based upon theory of change was developed to aid program considerations for future application cycles. CONCLUSIONS: PSPDs identified several benefits to virtual recruitment, including ease of accommodating increased applicants with a diverse applicant pool and enhanced faculty involvement. Identified limitations included reduced interaction between the applicant and the larger institution/city.

Study protocol of a multiphase optimization strategy trial (MOST) for delivery of smoking cessation treatment in lung cancer screening settings.

BACKGROUND: There is widespread agreement that the integration of cessation services in lung cancer screening (LCS) is essential for achieving the full benefits of LCS with low-dose computed tomography (LDCT). There is a formidable knowledge gap about how to best design feasible, effective, and scalable cessation services in LCS facilities. A collective of NCI-funded clinical trials addressing this gap is the Smoking Cessation at Lung Examination (SCALE) Collaboration. METHODS: The Cessation and Screening to Save Lives (CASTL) trial seeks to advance knowledge about the reach, effectiveness, and implementation of tobacco treatment in lung cancer screening. We describe the rationale, design, evaluation plan, and interventions tested in this multiphase optimization strategy trial (MOST). A total of 1152 screening-eligible current smokers are being recruited from 18 LCS sites (n = 64/site) in both academic and community settings across the USA. Participants receive enhanced standard care (cessation advice and referral to the national Quitline) and are randomized to receive additional tobacco treatment components (motivational counseling, nicotine replacement patches/lozenges, message framing). The primary outcome is biochemically validated, abstinence at 6 months follow-up. Secondary outcomes are self-reported smoking abstinence, quit attempts, and smoking reduction at 3 and 6 months. Guided by the Implementation Outcomes Framework (IOF), our evaluation includes measurement of implementation processes (reach, fidelity, acceptability, appropriateness, sustainability, and cost). CONCLUSION: We will identify effective treatment components for delivery by LCS sites. The findings will guide the assembly of an optimized smoking cessation package that achieves superior cessation outcomes. Future trials can examine the strategies for wider implementation of tobacco treatment in LDCT-LCS sites. TRIAL REGISTRATION: ClinicalTrials.gov NCT03315910.

A 10-Year Cross-Sectional Analysis of Public, Oncologist, and Patient Attitudes About Lung Cancer and Associated Stigma.

INTRODUCTION: Lung cancer stigma negatively impacts the clinical care and outcomes of those diagnosed, resulting in enduring disparities. The objective of this study was to determine whether attitudes toward lung cancer and the stigmatization of people diagnosed have changed over a decade. METHODS: A cross-sectional survey was administered to the general public, oncologists, and people with lung cancer 10 years apart (2008 and 2018) using the same instrument and methodology. The measures of stigma agreement ratings on a five-point Likert scale were compared between 2008 and 2018 for all three sample groups. RESULTS: In 2018, a total of 1001 members of the general public, 205 oncologists, and 208 people with lung cancer were enrolled. Improvements were noted over the decade, including the availability of more treatment options. Greater disease awareness was also found, with 94% of the public reporting knowledge of lung cancer (versus 82.5% in 2008, p < 0.0001). However, no change was found in the percentage of the public reporting that patients with lung cancer are at least partially to blame for their illness (60.3% in 2018). In 2018, more people with lung cancer agreed there is a stigma associated with lung cancer (72.1 versus 54.5%, p < 0.001) and that those diagnosed are viewed or treated differently by society in general (69.4% versus 50.8%, p < 0.001). CONCLUSIONS: The results reflect recognition of treatment gains and increased visibility of lung cancer but also highlight that stigma remains a significant problem. Of critical importance to the care of those diagnosed was the unexpected increase in stigma reported by the patient population.

Pilot Study of Peak Plasma Concentration After High-Dose Oral Montelukast in Children With Acute Asthma Exacerbations.

Acute asthma exacerbations are primarily due to airway inflammation and remain one of the most frequent reasons for childhood hospitalizations. Although systemic corticosteroids remain the mainstay of therapy because of their anti-inflammatory properties, not all inflammatory pathways are responsive to systemic corticosteroids, necessitating hospital admission for further management. Cysteinyl leukotrienes (LTs) are proinflammatory mediators that play an important role in systemic corticosteroids non-responsiveness. Montelukast is a potent LT-receptor antagonist, and an intravenous preparation caused rapid, sustained improvement of acute asthma exacerbations in adults. We hypothesized that a 30-mg dose of oral montelukast achieves peak plasma concentrations (Cmax ), comparable to the intravenous preparation (1700 ng/mL) and would be well tolerated in 15 children aged 5 to 12 years with acute asthma exacerbations. After administration of montelukast chewable tablets, blood samples were collected at 0, 15, 30, 45, 60, 120, 180, and 240 minutes. Plasma was separated and frozen at -80°C until analysis for montelukast concentration using liquid chromatography- tandem mass spectrometry. Median time to Cmax (tmax ) was 3.0 hours. Six participants (40%) achieved Cmax of 1700 ng/mL or higher. However, there was high interindividual variability in peak plasma concentration (median Cmax of 1378 ng/mL; range, 16-4895 ng/mL). No participant had side effects or adverse events. Plasma concentrations from this pilot study support the design of a weight-based dose-finding study aimed at selecting an optimal dose for future clinical trials to assess the efficacy of high-dose oral montelukast in children with moderate to severe asthma exacerbations.