Chronic Lung Research Articles

Late health effects and changes in lifestyle factors after cancer in childhood with and without subsequent second primary cancers - the KiKme case-control study.

Improved treatments for childhood cancer result in a growing number of long-term childhood cancer survivors (CCS). The diagnosis and the prevalence of comorbidities may, however, influence their lifestyle later in life. Nonetheless, little is known about differences in late effects between CCS of a first primary neoplasm (FPN) in childhood and subsequent second primary neoplasms (SPN) and their impact on lifestyle. Therefore, we aim to investigate associations between the occurrence of FPN or SPN and various diseases and lifestyle in the later life of CCS. CCS of SPN (n=101) or FPN (n=340) and cancer-free controls (n=150) were matched by age and sex, and CCS additionally by year and entity of FPN. All participants completed a self-administered questionnaire on anthropometric and socio-economic factors, medical history, health status, and lifestyle. Mean time between FPN diagnosis and interview was 27.3 years for SPN and 26.2 years for FPN CCS. To confirm results from others and to generate new hypotheses on late effects of childhood cancer as well as CCS´ lifestyles, generalized linear mixed models were applied. CCS were found to suffer more likely from diseases compared to cancer-free controls. In detail, associations with cancer status were observed for hypercholesterinemia and thyroid diseases. Moreover, CCS were more likely to take regular medication compared to controls. A similar association was observed for CCS of SPN compared to CCS of FPN. In contrast to controls, CCS rarely exercise more than 5 hours per week, consumed fewer soft and alcoholic drinks, and were less likely to be current, former, or passive smokers. Additionally, they were less likely overweight or obese. All other exploratory analyses performed on cardiovascular, chronic lung, inflammatory bone, allergic, and infectious diseases, as well as on a calculated health-score revealed no association with tumor status. CCS were more affected by pathologic conditions and may consequently take more medication, particularly among CCS of SPN. The observed higher disease burden is likely related to the received cancer therapy. To reduce the burden of long-term adverse health effects in CCS, improving cancer therapies should therefore be in focus of research in this area.

Low-frequency magnetotherapy with a running magnetic field of the POLYMAG-02M apparatus in the rehabilitation of patients after COVID-19

BACKGROUND: COVID-19 is an infectious viral disease caused by SARS-CoV-2 virus with high morbidity and mortality, especially among the elderly and those with concomitant factors such as diabetes mellitus, chronic lung and heart disease. For patients who have undergone coronavirus pneumonia, given the severity of the disease, rehabilitation measures are needed to restore the consequences of the disease.
 AIMS: To evaluate the effectiveness of the use of low-frequency magnetic therapy with a running magnetic field in the complex of rehabilitation treatment of patients who have undergone pneumonia caused by SARS-CoV-2 (COVID-19) at the stage of convalescence.
 MATERIAL AND METHODS: Examination and treatment of 42 patients (24 men and 18 women) aged 40 to 65 years, who had community-acquired pneumonia (J16.8) caused by the new coronavirus SARS-CoV-2 (COVID-19), were carried out. The first (main) group of patients included 22 people who underwent physical therapy, aeroinotherapy, low-frequency oscillatory massage of the chest in an electrostatic field, intravenous laser blood irradiation, high-frequency oscillation of the chest and carbon dioxide baths. Against this background, starting from the 20th day after discharge from the hospital, this group of patients received low-frequency, low-intensity magnetotherapy from the POLIMAG-02M apparatus. The second (control group) included 20 patients who received the same treatment, except for magnetotherapy from the POLIMAG-02M apparatus.
 RESULTS: The course of rehabilitation treatment led to an increase in the functional capabilities of the cardio-respiratory system in patients of both groups, an increase in chest excursions, an increase in the vital capacity of the lungs, the normalization of the act of breathing and ventilation of the lungs, and an improvement in the psychosomatic status of patients. In the main group, these changes are more pronounced than in the control group, which is associated with the inclusion of low-frequency magnetotherapy with a running magnetic field in the complex treatment.
 CONCLUSION: The use of low-frequency magnetic therapy with a running pulsed magnetic field in the complex of rehabilitation measures for patients who have undergone pneumonia caused by the COVID-19 virus significantly improves the somatic status of patients, increases exercise tolerance, and optimizes the function of external respiration. The data obtained make it possible to recommend the inclusion of the factor in clinical guidelines for the rehabilitation of patients who have undergone COVID-19.

Does Influenza Vaccination Reduce the Risk of Contracting COVID-19?

The concurrent timing of the COVID-19 pandemic and the seasonal occurrence of influenza, makes it especially important to analyze the possible effect of the influenza vaccine on the risk of contracting COVID-19, or in reducing the complications caused by both diseases, especially in vulnerable populations. There is very little scientific information on the possible protective role of the influenza vaccine against the risk of contracting COVID-19, particularly in groups at high-risk of influenza complications. Reducing the risk of contracting COVID-19 in high-risk patients (those with a higher risk of infection, complications, and death) is essential to improve public well-being and to reduce hospital pressure and the collapse of primary health centers. Apart from overlapping in time, COVID-19 and flu share common aspects of transmission, so that measures to protect against flu might be effective in reducing the risk of contracting COVID-19. In this study, we conclude that the risk of contracting COVID-19 is reduced if patients are vaccinated against flu, but the reduction is small (0.22%) and therefore not clinically important. When this reduction is analysed based on the risk factor suffered by the patient, statistically significant differences have been obtained for patients with cardiovascular problems, diabetics, chronic lung and chronic kidney disease; in all four cases the reduction in the risk of contagion does not reach 1%. It is worth highlighting the behaviour that is completely different from the rest of the data for institutionalized patients. The data for these patients does not suggest a reduction in the risk of contagion for patients vaccinated against the flu, but rather the opposite, a significant increase of 6%. Socioeconomic conditions, as measured by the MEDEA deprivation index, explain increases in the risk of contracting COVID-19, and awareness campaigns should be increased to boost vaccination programs.

Prevalence and predictors of depression, anxiety and stress among frontline healthcare workers at COVID-19 isolation sites in Gaborone, Botswana.

Coronavirus disease 2019 (COVID-19) has been associated with mental health outcomes and healthcare workers (HCWs) are at the highest risk. The aim of this study was to determine the prevalence and predictors of depression, anxiety and stress, among frontline HCWs at COVID-19 isolation and treatment sites in Gaborone, Botswana. This was a cross-sectional study using self-administered questionnaires at the six (6) isolation facilities. The 42-item Depression, Anxiety and Stress Scale (DASS-42) was used to assess for the outcomes. The proportions are presented with 95% confidence intervals (95% CI). Logistic regression analysis identified predictors of the outcomes. A p value of <0.05 was considered significant. A total of 447 participants with a median age of 30 years responded. Depression, anxiety and stress were detected in 94 (21.0% (95% CI 17.3-25.1%)), 126 (28.2% (CI 24.1-32.6%)) and 71 (15.9% (12.6-19.6%)) of the participants respectively. Depression was associated with smoking (AOR 2.39 (95% CI 1.23-4.67)), working at the largest COVID-19 isolation centre, Sir Ketumile Masire Teaching Hospital (SKMTH) (AOR 0.25 (95% CI 0.15-0.43)) and experience of stigma (AOR 1.68 (95% CI 1.01-2.81)). Tertiary education (AOR 1.82 (95% CI 1.07-3.07)), SKMTH (AOR 0.49 (95% CI 0.31-0.77)), household members with chronic lung or heart disease (AOR 2.05 (95% CI 1.20-3.50)) and losing relatives or friends to COVID-19 (AOR 1.72 (95% CI 1.10-2.70)) were predictors of anxiety. Finally, predictors of stress were smoking (AOR 3.20 (95% CI 1.42-7.39)), household members with chronic heart or lung disease (AOR 2.44 (95% CI 1.27-4.69)), losing relatives or friends to COVID-19 (AOR 1.90 (1.05-3.43)) and working at SKMTH (AOR 0.24 (0.12-0.49)). Depression, anxiety and stress are common among frontline HCWs working in the COVID-19 isolation sites in Gaborone. There is an urgent need to address the mental health outcomes associated with COVID-19 including addressing the risk factors identified in this study.

Readmission Following Perioperative Myocardial Injury: Clinical Predictors and Impact on Mortality.

Background Perioperative myocardial injury (PMI) following noncardiac surgery is associated with a high risk for mortality, and readmission within 30 days of PMI increases this risk. Identifying risk factors for readmission among survivors of PMI is critical to improving outcomes in PMI. We examined risk factors for readmission following discharge after surgery complicated by PMI and the effect of readmission on 1-year mortality. Methods The study is a retropective cohort analysis of patients diagnosed with PMI in a single health system over a 10-year period. Univariate predictors of readmission were used to construct a multivariable logistic regression model. Mortality was assessed using Kaplan–Meyer survival analysis. Results Of the 207,729 surgical patients, 5159 (2.5%) had PMI. By 30 days following PMI, 1254 patients (24.3%) died, 1142 (22.2%) were readmitted but alive at 30 days, and 2763 patients (53.5%) were alive and had not been readmitted. Readmitted patients were older, had higher peak troponin levels, and were more likely to have prior coronary, neoplastic, lung, and kidney disease. Multivariable logistic regression revealed increasing age and peak troponin, prior cancer diagnosis, and chronic lung and kidney disease as independent predictors of readmission. Readmitted patients had higher 1-year mortality than those not readmitted (33.9% vs. 22.2%, p < 0.001). Conclusions Readmission following PMI is associated with increased mortality in the following year. Patients suffering from PMI who are at risk of readmission are older, have a greater extent of myocardial injury, and are more likely to have chronic comorbidities. Identification of patients at risk of readmission following PMI is critical to improving both outcomes and utilization of hospital resources.

Effect of Comorbidities on Inflammatory Bowel Disease-Related Colorectal Cancer: A Nationwide Inpatient Review.

Introduction The risk of inflammatory bowel disease-associated colorectal cancer (IBD-CRC) is known to increase with primary sclerosing cholangitis (PSC) and a family history of CRC. However, the impact of comorbidities such as liver disease, obesity, diabetes, chronic lung, heart, and renal disease, and psychiatric illness on the risk of IBD-CRC remains unclear. We evaluated the effect of these comorbidities on the risk of IBD-CRC.MethodsA retrospective review from 2009 to 2014 was conducted using the National Inpatient Sample data for adults 18 years and older. Patients with IBD (360,892), of whom 2,831 had CRC were identified using the International Classification of Diseases, Ninth Revision codes (ICD-9). Data on comorbidities were also obtained. Adjusted odds ratios (aOR) and confidence intervals (CI) were computed via logistic regression to evaluate the effect of comorbidities on the risk of IBD-CRC; the p-value was set at <0.05.ResultsThe mean age of IBD patients in this study was 52.36±0.03. A majority of the patients with IBD-CRC were white and were significantly older compared to those without cancer (60 vs 52 years, p<0.05). The risk of colon cancer in IBD was increased by having a non-cholestatic liver disease (aOR 1.51, CI 1.23-1.86, p<0.01). Also, patients younger than 50 years with liver disease were at an increased risk of IBD-associated colon cancer in comparison to older patients (aOR 1.83 vs 1.34, p<0.05). Notably, diabetes, chronic pulmonary disease, renal failure, psychiatric illnesses, and rheumatoid diseases, were inversely associated with the risk of IBD-CRC (p<0.05). After stratifying by IBD subtypes, non-cholestatic liver disease was still independently associated with a higher risk for colon cancer in patients with ulcerative colitis or Crohn's disease (ulcerative colitis: aOR 1.43, CI 1.08-1.89; Crohn's disease: aOR 1.46, CI 1.10-2.00).ConclusionsPatients with IBD who have non-cholestatic liver disease might have a higher risk for colon cancer, even at a younger age. These patients may require close colon cancer surveillance.

Cardiovascular outcomes of COVID-19 disease at the elderly

Background and Aims : Covid-19 disease can cause multiple organ damages. Male gender, advanced age, chronic lung, kidney and cardiovascular diseases have been identified as risk factors for severity of the disease. The persisting alterations of the heart for more than four weeks is framed in post-Covid-19 syndrome. Cardiovascular system is affected by direct effect of Sars-Cov-2, as well as by preexistent frailty.

The Prevalence of Multimorbidity among Foreign-born Adults in the United States.

We examined multimorbidity among foreign-born adults in the United States. This population may be particularly affected by chronic conditions and limited health care access. Longitudinal cohort. United States. Foreign-born adults at the point of legal permanent residency. Multimorbidity defined as two or more of eight chronic conditions (hypertension, diabetes, obesity, arthritis, stroke, cancer, chronic lung disease, and heart problems). We estimated the prevalence of multimorbidity and patterns over time. Data are from the New Immigrant Survey (NIS), a nationally representative study of adult immigrants at green card status in 2003 (N=8,174) and reinterview in 2008. The prevalence of multimorbidity was 6% in 2003, and 12% in 2008. The most common condition dyad at both time points was hypertension-obesity; the largest increase over time was in combinations that included hypertension, diabetes, and obesity. The odds of having multimorbidity compared to no chronic conditions were higher among older immigrants and those who had seen a doctor in the past year. The odds of gaining one chronic condition over a 5-year period increased with age; 45-65 years: OR 2.8[CI 2.3,3.5]; aged ≥65 years: OR 3.2 CI[2.2,4.7]. The prevalence of multimorbidity among immigrants was lower than the prevalence in the overall US population of the same age, consistent with studies showing an immigrant health advantage.

Indicators of lung function in children with chronic nonspecific lung diseases with pulmonary fibrosis

Introduction. The pathogenesis of most chronic nonspecific lung diseases (CNSLD) in children is based on a long-term inflammatory process, often leading to the formation of pulmonary fibrosis in the structurally altered tissue, which requires dynamic monitoring of patients, including the study of lung function.Aim. To assess the indicators of the lung function in children with chronic bronchopulmonary pathology accompanied by pulmonary fibrosis.Materials and methods. 84 children with CNSLD were examined. The main group consisted of 45 children with CNSLD with pulmonary fibrosis (bronchopulmonary dysplasia, congenital malformations of the lungs, chronic bronchitis, and post pneumonia fibrosis). The comparison group consisted of 39 children with CNSLD without pulmonary fibrosis. The average age of children in the study groups was 9,3±0,48 years. The patients underwent multispiral computed tomography of the lungs with a virtual bronchoscopy program and intravenous bolus contrast enhancement. Evaluation of lung function was carried out by spirometry.Results. In patients in remission, the average values of the ventilation capacity of the lungs in both groups were within the predicted values. However, in patients with fibrotic changes, pulmonary dysfunction was detected 2 times more often than in children with CNSLD without pulmonary fibrosis (35.5% and 15.4%, respectively, p&lt;0.05). Restrictive ventilation disorders were diagnosed only in the group of patients with pulmonary fibrosis. In children with pulmonary fibrosis, the risk of reduced ventilation capacity is significantly higher than in children with CNSLD without pulmonary fibrosis (OR=3.04, 95% CI 1.049–8.78).Conclusion. The data obtained can serve as a prerequisite for further development of predicting the nature of the course of the disease, identifying “risk groups” for the development of fibrotic changes for a personalized approach to the treatment and follow-up of patients with CNSLD.

ISM1 suppresses LPS-induced acute lung injury and post-injury lung fibrosis in mice

BackgroundAcute lung injury/acute respiratory distress syndrome (ALI/ARDS) are clinical syndromes characterized by acute lung inflammation, pulmonary edema and hypoxemia, with up to 50% mortality rate without effective pharmacological therapy. Following the acute inflammation, repair and remodeling occurs which in some cases resulting in lung fibrosis. The pathophysiology of ALI/ARDS remains incompletely understood. Lipopolysaccharide (LPS)-induced ALI in mice have been widely used as a model to study human ALI/ARDS. Isthmin 1 (ISM1) is a secreted protein highly abundant in mouse lung. We have previously reported that upon intratracheal LPS instillation, ISM1 expression in the lung is further upregulated. Recently, we also reported that ISM1 is an anti-inflammatory protein in the lung with Ism1-/- mice presenting spontaneous chronic low-grade lung inflammation and obvious emphysema at young adult stage. However, what role ISM1 plays in ALI/ARDS and lung fibrosis remain unclear.MethodsUsing Ism1-/- mice and intratracheal LPS-induced ALI, and local delivery of recombinant ISM1 (rISM1), we investigated the role ISM1 plays in ALI and post-ALI lung fibrosis using flow cytometry, Western blot, antibody array, immunohistochemistry (IHC), immunofluorescent and other histological staining.ResultsWe reveal that ISM1 deficiency in mice led to an intensified acute lung inflammation upon intratracheal LPS challenge, with a heightened leukocyte infiltration including neutrophils and monocyte-derived alveolar macrophages, as well as upregulation of multiple pro-inflammatory cytokines/chemokines including tumor necrosis factor α (TNF-α). Although innate immune cells largely subsided to the baseline by day 7 post-LPS challenge in both wild-type and Ism1−/− mice, Ism1−/− lung showed increased post-ALI fibrosis from day 9 post-LPS treatment with increased myofibroblasts, excessive collagen accumulation and TGF-β upregulation. The heightened lung fibrosis remained on day 28 post-LPS. Moreover, intranasal delivered recombinant ISM1 (rISM1) effectively suppressed LPS-induced acute lung inflammation and ALI, and rISM1 suppressed LPS-induced NF-κB activation in cultured mouse alveolar macrophages.ConclusionTogether with our previous report, this work further established ISM1 as an endogenous anti-inflammation protein in the lung, restraining excessive host inflammatory response to LPS-triggered ALI and suppressing post-ALI lung fibrosis likely through suppressing NF-κB activation and pro-inflammatory cytokine/chemokine production.

Abstract 5024: Aging patterns in five disparate cancer entities indicate a novel senescent cell population with therapeutic targetability

Abstract Human aging is associated with molecular changes and cellular degeneration, resulting in a significant increase in cancer incidence with age. Whether aging as its own entity can be initiator of putative cancerous developments, the transcriptional changes underlying the cancerous development itself are largely unknown. Here, we analyzed publicly available bulk RNA sequencing data of 328 control vs. 453 cancer samples in combination with single cell sequencing datasets from 49 control vs. 105 cancer patients. Using widely accepted aging-associated gene sets, we assembled key features of aging and their reflection in cancer development in five distinct cancer entities with an age-dependent increase of incidence, i.e. chronic myeloid leukemia (CML), colorectal cancer (CRC), hepatocellular carcinoma (HCC), lung cancer (LC) and pancreatic ductal adenocarcinoma (PDAC). After confirmation of the aging/senescence-induced gene (ASIG) expression to be upregulated in malignant diseases compared to healthy controls, we elucidated the importance of ASIGs during single cell development, making use of pseudotime analyses. In each entity, distinct temporally late enrichment states were carved out, and their transcriptional connectivity next to epigenetic control verified. Remarkably, we were able to demonstrate that all cancer entities analyzed in this study comprised cell populations expressing ASIGs. Except for pancreatic cancer, all entities accounted for subpopulations with aging associated patterns. Using a novel pipeline to repurpose FDA-approved drugs and combinations on a single cell level, we discovered a path for novel treatment regimen on a tumor-specific basis. These respective cellular subpopulations demonstrate pillars of susceptibility within the complex tumor microenvironment and serve as a basis for future studies on the role of aging and senescence in human malignancies. Citation Format: Dominik Saul, Robyn Laura Kosinsky. Aging patterns in five disparate cancer entities indicate a novel senescent cell population with therapeutic targetability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5024.

Abstract 1032: Progesterone receptor antagonist can provide marked palliative benefits and extend life by years in advanced lung cancer when no other treatment options are available

Abstract Metastatic lung cancer has a poor prognosis. The aim of chemotherapeutic agents, targeted therapies, or immunotherapies at this stage is to extend life and diminish suffering. Frequently the extension of life is for a few months, but amelioration of suffering is not always accomplished including side effects of medication. Mifepristone, a progesterone (P) receptor modulator/antagonist has been given to patients orally (200-300 mg/day) with Food and Drug Administration (FDA) approval to patients with advanced metastatic lung cancer that had no more treatment options. Several of these cases have been presented at the AACR and showed significant extension of a good quality of life with well tolerated mifepristone therapy (Case 1 - rapidly progressing probable small cell lung cancer (SCLC) with marked hypoxia and marked hyponatremia, AACR 2016; Case 2 - Stage IV non-small cell lung cancer (NSCLC) with brain metastasis with no tumor markers for targeted therapy, AACR 2017; Case 3 - NSCLC positive for programmed cell death protein 1 (PD-1), AACR 2018). In case 1 her PO2 and serum sodium normalized within 3 weeks of single agent mifepristone and her lung nodules were no longer detectable. At time of presentation in 2016 she was 3 ½ years on single agent mifepristone treatment. She died 5 years from treatment at age 85 from a myocardial infarction with no return of her lung cancer and normal serum sodium. Case 2 also received single agent mifepristone and had no new lung or brain lesions (predominantly stable disease), but he stated he felt perfectly normal. After 2 ½ years his primary lung lesion started growing slowly. He died 5 years later not from extensive lung cancer but from pneumonia complicating his chronic obstructive lung disease (COPD). Case 3 had progressed despite standard chemotherapy and nivolumab. With mifepristone her lung and brain metastases showed some regression, but she was enjoying a good quality of life. Her clinical status deteriorated after 1 year not from her cancer but worsening COPD and she died 1 ½ years after initiating mifepristone therapy. Two female cases (age 56 and 46) that were never presented at AACR were treated with mifepristone when their advanced lung cancer with brain metastases progressed despite the third-generation tyrosine kinase inhibitor osimertinib (they were positive for the EGFR mutation). These women had a good quality of life and are still alive after 4 years of treatment. Evidence suggests that mifepristone inhibits cancer by blocking membrane P receptors inhibiting the immunosuppressive protein called the progesterone induced blocking factor. The “parent” 90 kDa form helps the tumor to proliferate and invade normal tissue whereas smaller splice variants inhibit cellular immunity. Mifepristone may actually be more effective for cancers negative for the classical nuclear P receptor. Citation Format: Jerome H. Check, Diane Check, Trina Poretta. Progesterone receptor antagonist can provide marked palliative benefits and extend life by years in advanced lung cancer when no other treatment options are available [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1032.

Een bacterie vermomd als schimmel: pulmonale actinomycose bij een geriatrische patiënte

A bacteria masked as a fungus: a case of pulmonary actinomycosis in a geriatric patient Pulmonary actinomycosis is a relatively rare diagnosis which probably results from the aspiration of oropharyngeal or gastrointestinal secretions. Individuals with aspiration, alcoholism, poor oral hygiene, chronic obstructive lung disease and a decreased immune response are at risk. The most common symptoms are nonspecific and often present late. The imaging of pulmonary actinomycosis is not specific. Therefore, the disease is frequently confused with a malignancy or tuberculosis. The gold standard for the diagnosis is a histological examination and bacterial culture of a lung biopsy. Its treatment requires high doses of penicillin during at least 3 months. In this article, the case of an 82-year-old patient with malaise but without any respiratory complaints is presented. Further examination revealed inflammatory blood signs, as well as infiltration of the right upper lobe on a CT scan of the thorax. To exclude an underlying malignancy, a bronchoscopy was performed. Gram staining of the bronchoalveolar washing showed gram-positive branching rods suspicious for Actinomyces species. Histological examination confirmed the diagnosis of pulmonary actinomycosis. By means of an antibiotic treatment with amoxicillin the patient recovered both clinically and biochemically.

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease of unknown origin. It is characterized by aberrant scarring of the alveolar epithelium leading to an accumulation of extracellular matrix (ECM). Fibroblastic foci, consisting of fibroblasts and myofibroblasts, are responsible for the excessive production of ECM. The two therapeutic molecules available on the market to date only allow to slow down the evolution of the disease. In this review, we present the mechanisms involved in the progression of the disease, its treatments and the study models.

P129 Evidence for a role of Achromobacter xylosoxidans VBNC forms in chronic cystic fibrosis lung infection

P129 Evidence for a role of Achromobacter xylosoxidans VBNC forms in chronic cystic fibrosis lung infection

P130 Achromobacter spp. phenotypic differences between chronic and occasional lung infection in cystic fibrosis

P130 Achromobacter spp. phenotypic differences between chronic and occasional lung infection in cystic fibrosis

Social determinants of health in a prospective study of whole-exome sequencing in advanced cancer patients from underserved communities.

e18539 Background: Social determinants of health (SDOH) influence outcomes of oncologic care and more data are needed to understand these factors in underserved communities. At the same time, disparities in access to genomic tests and genomic databases that overrepresent European ancestry may contribute to disparities in precision oncology. We established a prospective study incorporating SDOH assessments and whole exome sequencing for advanced cancer patients in underserved communities. Methods: In this ongoing multi-center, prospective, observational study involving community oncology practices in underserved communities, patients with advanced cancers received whole exome/whole transcriptome sequencing and hereditary cancer testing (Sema4, Stamford, CT). Patients also completed an enrollment questionnaire focused on SDOH. The study began enrollment in July 2021 at a community practice in South Carolina and has expanded to a second practice in North Carolina as of February 2022. This report describes demographic and SDOH characteristics of patients enrolled at the first site between 7/2021-2/2022. Results: A total of 161 enrolled patients have completed baseline demographics. SDOH data are available for 148 (91.9%) patients. The cohort was predominantly female (N = 99, 61.5%), with 34 (21.1%) patients reporting Black race, and a mean age of 65.5 years (s.d. 14.2). Three patients (0.02%) reported Hispanic ethnicity. The most common cancer types in the cohort were breast (N = 37, 23.0%), chronic lymphocytic leukemia (N = 18, 11.2%), colorectal (N = 13, 8.1%), myelodysplastic syndrome (N = 12, 7.5%), and non-small cell lung cancer (N = 11, 6.8%). In terms of SDOH factors, 64 (43.2%) patients reported household incomes &lt; $25,000 and the majority reported household incomes &lt; $50,000 (N = 93, 57.8%). A minority of patients had 4-year college degrees or higher (N = 36, 24.3%); the highest educational attainment was high school graduate for most (N = 70, 47.3%). Household income &lt; $50,000 was associated with financial and food insecurity: patients from lower-income households were more likely to report being worried about being able to pay bills often/always (19.4% vs. 0%, Fisher’s exact p = 0.03) and were more likely to have either worried about running out of food (18.3% vs. 0%, Fisher’s exact p = 0.02) or to have run of out of food (15.1% vs. 0%, Fisher’s exact p = 0.02) in the past 12 months. Conclusions: Among advanced cancer patients in an underserved community, lower household income was associated with both financial and food insecurity. This ongoing observational study will integrate SDOH, genomic characteristics, and clinical outcomes from a diverse cohort of patients seen in community oncology practices.

Overall survival of patients with chronic obstructive pulmonary disease receiving immunotherapy for non-small cell lung cancer: A population-based analysis in Ontario, Canada.

e21172 Background: Outside of clinical trial eligibility criteria, there is limited data to guide the selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) therapy. Chronic obstructive pulmonary disease (COPD) and lung cancer are associated, independent of smoking history, with a common background of chronic inflammation. Previous studies have demonstrated that COPD is a negative prognostic marker for NSCLC, but the clinical benefit of ICI in patients with NSCLC and COPD is unknown. Methods: A population-level administrative data analysis of Ontario patients was performed through the Institute of Clinical Evaluative Sciences (ICES) Data Analytic Services. All patients with NSCLC diagnosed between Jan 2010 and Dec 2020 and treated with immune-checkpoint inhibitors (pembrolizumab, nivolumab, atezolizumab) were included. Demographics, comorbidity and marginalization scores, and COPD status were extracted along with outcome information. Overall survival (OS) was estimated using the Kaplan-Meier method, and compared between patients with or without COPD using Cox proportional hazards regression. The frequency of patients requiring hospitalization and duration of treatment was also estimated and compared using the chi-square and Wilcoxon rank-sum test. Results: 73331 NSCLC patients were identified, of which 4.5% (n = 3285) patients received ICI. COPD patients were less likely to receive immunotherapy (3.8% vs. 5.1%, p &lt; 0.001). Among those receiving an ICI, 41% (n = 1362) of patients had a diagnosis of COPD prior to NSCLC diagnosis. Median (95% CI) OS was 17.3 (16.6 to 18.2) months for patients with COPD and 16.9 (16.2 to 17.8) for patients with no known COPD, which was not significantly different in univariate (hazard ratio = 0.96, 95% CI = 0.89 to 1.04, p = 0.35) or multivariate analysis (HR = 0.96, 95% CI = 0.89 to 1.05, p = 0.40). The 5-year survival was also similar between both groups (6.7% vs. 6.5%). The rate of hospitalization within 6 months (18.4% vs 18.0%, p = 0.82) and the duration of immunotherapy treatment (median = 80 vs 71 days p = 0.23) did not differ for the COPD vs. non-COPD groups. Conclusions: Despite an expectation of frailty, our data suggest that NSCLC patients with COPD receiving ICI maintained similar durations of treatment and similar rates of hospitalization, with no significant difference in survival time, compared with those without COPD. While a treatment selection bias cannot be excluded in this non-randomized dataset, our data suggest that a diagnosis of COPD itself should not be considered a contraindication to immune checkpoint inhibitor use in NSCLC.

Lack of Association between Inhaled Corticosteroid Use and the Risk of Future Exacerbation in Patients with GOLD Group A Chronic Obstructive Pulmonary Disease.

Background: As most clinical trials have been performed in more symptomatic and higher-risk patients, evidence regarding treatment in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A chronic obstructive pulmonary disease (COPD) is limited. We assessed the distribution of inhaler treatment and sought to investigate the association between inhaled corticosteroid (ICS) use and future exacerbation in GOLD group A COPD patients. Methods: Patients with GOLD group A COPD who received maintenance inhalers were identified from a multicentre, prospective cohort in South Korea. Patients were categorized as group A when they had fewer symptoms and did not experience severe exacerbation in the previous year. Development of moderate or severe exacerbation during the 1-year follow-up was analysed according to baseline inhaler treatment. Results: In 286 patients with GOLD group A COPD, mono-bronchodilator (37.8%), dual-bronchodilator (29.0%), triple therapy (17.5%), and ICS/long-acting beta-2 agonist (15.4%) were used. Compared to patients without ICS-containing inhalers (N = 191), those using ICS (N = 95) were more dyspnoeic, and more likely to have asthma history, lower lung function, and bronchodilator response. During the 1-year follow-up, moderate or severe exacerbations occurred in 66 of 286 (23.1%) patients. In the multivariable logistic regression analysis, ICS-containing inhaler use was not associated with the development of exacerbation, even in the subgroup with a high probability of asthma–COPD overlap. Conclusion: Although about one-third of patients with GOLD group A COPD were using ICS-containing inhalers, use of ICS was not associated with a reduction in the future development of exacerbation.

JMM Profile: Achromobacter xylosoxidans: the cloak-and-dagger opportunist.

Achromobacter xylosoxidans is associated with resilient nosocomial infections, with bacteraemia, pneumonia and chronic cystic fibrosis lung infection being the most common clinical presentations. Innate multi-drug resistance and a suite of virulence factors select for A. xylosoxidans infection during long-term antibiotic therapy, contributing to its persistence, treatment recalcitrance, association with poor clinical outcomes and emergence as a problematic pathogen. Horizontal gene transfer and maintenance of large genomes underpin the resilience and cosmopolitan lifestyle of A. xylosoxidans, and complicate its phylogenetic characterization.