Risk Factors For Lung Disease Research Articles

Welding Fumes Versus Respiratory System – An Up-to-Date Overview of Welding Lung Diseases

Abstract Welding processes generate significant occupational contaminants, including particulate matter, metal fumes, and gas by-products. Exposure to these fumes can lead to various health issues in welders. This article emphasizes the need for preventive measures to improve the health of welders and reduce the risks associated with welding.The study explores the impact of welding fumes on the respiratory system and occupational lung disease. It identifies the inhalation of welding fumes as a significant risk factor for lung disease, and the need for clear limitations on welding fume exposure. The research also highlights the importance of understanding the mechanisms underlying lung conditions caused by welding fumes. The study concludes by including 30 citations from several databases (Google Scholar, ResearchGate, MDPI and AcademiaEdu) to raise awareness and establish a scientific link between welding fumes and oral health and teeth structure. The inhalation of welding fumes can significantly impact the respiratory system, causing concerns about safety measures and guidelines for welding environments. Exposure to harmful substances like welding fumes can also affect the oral cavity, a part of both digestive and respiratory system, and therefore, the impact on teeth hard structures claims further scientific investigations.

Regulation of lung inflammation by adiponectin.

Adiponectin is an insulin sensitizing hormone that also plays a role in the regulation of inflammation. Although adiponectin can exert pro-inflammatory effects, more studies have reported anti-inflammatory effects, even in non-adipose tissues such as the lung. Obesity is considered an inflammatory disease, is a risk factor for lung diseases, and is associated with decreased levels of plasma adiponectin. The results of recent studies have suggested that adiponectin exerts anti-inflammatory activity in chronic obstructive pulmonary disease, asthma and invasive fungal infection. The signaling receptors of adiponectin, AdipoR1 and AdipoR2, are expressed by epithelial cells, endothelial cells, and immune cells in the lung. In this mini-review, we discuss the anti-inflammatory mechanisms of adiponectin in lung cells and tissues.

Abstract 6465: Associations of early menopause and hormone therapy with lung health and mortality among female never and ever smokers from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Abstract Our previous study using the Lovelace Smokers cohort identified early natural menopause (i.e., age at menopause<45 yr), which is a biomarker of ovarian aging, as a risk factor for lung disease and mortality among female smokers. However, most of the associations reported in female smokers with natural menopause were not observed in those with surgical menopause, (a mixed group of subjects with bilateral oophorectomy or hysterectomy without bilateral oophorectomy). Females with bilateral oophorectomy lose ovarian estrogen and progesterone production, while females with hysterectomy, +/- unilateral oophorectomy, maintain some of this hormone production. We hypothesize that associations between early menopause, lung health and mortality will vary based on type of menopause. Among 69,071 females from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, early menopause rates were 8.7%, 44.1%, and 72.8% in never smokers versus 12.1%, 51.6%, and 78.0% in ever smokers with natural, bilateral oophorectomy, or hysterectomy without bilateral oophorectomy, respectively. We analyzed the associations of early menopause and hormone therapy with lung health (physician diagnosed emphysema and chronic bronchitis and lung cancer incidence) and mortality (all-cause and cause-specific) outcomes by smoking status and menopause types. The most consistent associations were observed for all-cause mortality: 1) Except in never smokers who received hysterectomy only, early menopause was associated with higher all-cause mortality regardless of smoking status 2) hormone therapy was associated with lower all-cause mortality in all groups and the longer the use, the more beneficial the outcome; 3) the magnitude of this association was strongest in those who underwent bilateral oophorectomy. Furthermore, in ethnic disparity analysis, all-cause mortality was affected by early menopause to a lesser degree in non-Hispanic black ever smokers and there was increased benefit from hormone therapy in non-Hispanic black never smokers. Overall, we identified further evidence supporting early menopause as a risk factor for lung health and mortality and hormone therapy as being beneficial regardless of smoking status or menopause type. Our results support the “shorter lifetime estrogen exposure in early menopause” hypothesis and the clinical importance of hormone therapy beyond withdrawal symptom coping. Supported by National Cancer Institute (NCI) grant P30 CA118100. The authors thank the NCI for access to NCI's data collected by the PLCO Cancer Screening Trial (the Cancer Data Access System Project Number PLCO-981). Citation Format: Tessa Flores, Xiaochun Gai, Yiliang Zhu, Kimberly Leslie, Shuguang Leng. Associations of early menopause and hormone therapy with lung health and mortality among female never and ever smokers from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6465.

Alcohol use disorder as a potential risk factor for COVID-19 severity: A narrative review.

In Dec. 2019-January 2020, a pneumonia illness originating in Wuhan, China, designated as coronavirus disease 2019 (COVID-19) was shown to be caused by a novel RNA coronavirus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). People with advanced age, male sex, and/or underlying health conditions (obesity, type 2 diabetes, cardiovascular disease, hypertension, chronic kidney disease, and chronic lung disease) are especially vulnerable to severe COVID-19 symptoms and death. These risk factors impact the immune system and are also associated with poor health, chronic illness, and shortened longevity. However, a large percent of patients without these known risk factors also develops severe COVID-19 disease that can result in death. Thus, there must exist risk factors that promote exaggerated inflammatory and immune response to the SARS-CoV-2 virus leading to death. One such risk factor may be alcohol misuse and alcohol use disorder because these can exacerbate viral lung infections like SARS, influenza, and pneumonia. Thus, it is highly plausible that alcohol misuse is a risk factor for either increased infection rate when individuals are exposed to SARS-CoV-2 virus and/or more severe COVID-19 in infected patients. Alcohol use is a well-known risk factor for lung diseases and ARDS in SARS patients. We propose that alcohol has three key pathogenic elements in common with other COVID-19 severity risk factors: namely, inflammatory microbiota dysbiosis, leaky gut, and systemic activation of the NLRP3 inflammasome. We also propose that these three elements represent targets for therapy for severe COVID-19.

Microplastics, potential threat to patients with lung diseases.

Air pollution is one of the major risk factors for lung disease. Microplastics are a ubiquitous environmental pollutant, both indoors and in outdoor air. Microplastics have also been found in human lung tissue and sputum. However, there is a paucity of information on the effects and mechanisms of microplastics on lung disease. In this mini-review, we reviewed the possible mechanisms by which air microplastics’ exposure affects lung disease and, at the same time, pointed out the limitations of current studies.

Validation of in vitro models for smoke exposure of primary human bronchial epithelial cells.

The bronchial epithelium is constantly challenged by inhalative insults including cigarette smoke (CS), a key risk factor for lung disease. In vitro exposure of bronchial epithelial cells using CS extract (CSE) is a widespread alternative to whole CS (wCS) exposure. However, CSE exposure protocols vary considerably between studies, precluding direct comparison of applied doses. Moreover, they are rarely validated in terms of physiological response in vivo and the relevance of the findings is often unclear. We tested six different exposure settings in primary human bronchial epithelial cells (phBECs), including five CSE protocols compared with wCS exposure. We quantified cell-delivered dose and directly compared all exposures using expression analysis of 10 well-established smoke-induced genes in bronchial epithelial cells. CSE exposure of phBECs was varied in terms of differentiation state, exposure route, duration of exposure, and dose. Gene expression was assessed by quantitative real-time PCR (qPCR) and Western Blot analysis. Cell type-specific expression of smoke-induced genes was analyzed by immunofluorescent analysis. Three surprisingly dissimilar exposure types, namely, chronic CSE treatment of differentiating phBECs, acute CSE treatment of submerged basal phBECs, and wCS exposure of differentiated phBECs performed best, resulting in significant upregulation of seven (chronic CSE) and six (acute wCS, acute submerged CSE exposure) out of 10 genes. Acute apical or basolateral exposure of differentiated phBECs with CSE was much less effective despite similar doses used. Our findings provide guidance for the design of human in vitro CS exposure models in experimental and translational lung research.

Electronic cigarette use and its association with asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome among never cigarette smokers.

INTRODUCTIONAlthough smoking is a strong risk factor for lung diseases including asthma, COPD, and asthma-COPD overlap syndrome (ACOS), studies are needed to examine the association between e-cigarettes and asthma, COPD, and ACOS. This study evaluated the association between e-cigarette use and self-reported diagnosis of asthma, COPD, and ACOS using a large nationally representative sample of adults aged ≥18 years in the United States.METHODSCross-sectional data from the Behavioral Risk Factor Surveillance System (BRFSS) from 2016 to 2018 were used to examine self-reported information on current e-cigarette use, demographic variables, and asthma and COPD status among never cigarette smokers (n=8736). Asthma and COPD were measured by self-reported diagnosis, and respondents who reported having both diagnoses were then classified as having ACOS. Of the 469077 never cigarette smokers, 4368 non-e-cigarette users were 1:1 propensity score-matched to e-cigarette users on age, sex, race/ethnicity and education level. We used multinomial logistic regression to examine association between current e-cigarette use and self-report asthma, COPD, and ACOS while controlling for marital status and employment in addition to matching variables.RESULTSCompared with never e-cigarette users, e-cigarette users had increased odds of self-reported ACOS (OR=2.27; 95% CI: 2.23–2.31), asthma (OR=1.26; 95% CI: 1.25–1.27) and COPD (OR=1.44; 95% CI: 1.42–1.46).CONCLUSIONSOur findings suggest that e-cigarette use is associated with an increased odds of self-reported asthma, COPD, and ACOS among never combustible cigarette smokers. BRFSS provides cross-sectional survey data, therefore a causal relationship between e-cigarette use and the three lung diseases cannot be evaluated. Future longitudinal studies are needed to validate these findings.

Short Communication: A Pilot Study of the Effects of Losartan Versus Placebo on Pneumoproteins in HIV: A Secondary Analysis of a Randomized Double Blind Study.

HIV is an independent risk factor for lung disease, including chronic obstructive pulmonary disease (COPD) and emphysema. Angiotensin receptor blockers may be beneficial in COPD and emphysema through pathways that have been implicated in HIV-related lung disease. We performed a randomized comparison of the effects of losartan versus placebo on the plasma concentrations of the pneumoproteins, surfactant protein D (SPD) and club cell secretory protein (CCSP), in people living with HIV (PLWH). A total of 108 PLWH were included (52 assigned to losartan and 56 assigned to placebo). We found no difference in the change from baseline in log2 concentrations of CCSP or SPD over 1 year of follow-up. For SPD, we found a strong interaction by CD4+ counts, where those with CD4+ counts >350 cells/mm3 treated with losartan had more reduction (improvement) in SPD concentration than those treated with placebo (p value for interaction <.001). In conclusion, we did not find a beneficial effect of losartan on pneumoprotein concentrations in PLWH, but PLWH with higher CD4+ counts may have improvement in SPD when treated with losartan.

Electronic cigarette use and its association with asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome among never cigarette smokers.

INTRODUCTIONAlthough smoking is a strong risk factor for lung diseases including asthma, COPD, and asthma-COPD overlap syndrome (ACOS), studies are needed to examine the association between e-cigarettes and asthma, COPD, and ACOS. This study evaluated the association between e-cigarette use and self-reported diagnosis of asthma, COPD, and ACOS using a large nationally representative sample of adults aged ≥18 years in the United States.METHODSCross-sectional data from the Behavioral Risk Factor Surveillance System (BRFSS) from 2016 to 2018 was used to examine self-reported information on current e-cigarette use, demographic variables, and asthma and COPD status among never cigarette smokers (n=8736). Asthma and COPD were measured by self-reported diagnosis, and respondents who reported having both diagnoses were then classified as having ACOS. Of the 46079 never cigarette smokers, 4368 non-e-cigarette smokers were 1:1 propensity score-matched to e-cigarette smokers on age, sex, race/ethnicity and education level. We used multinomial logistic regression to examine association between current e-cigarette use and self-report asthma, COPD, and ACOS while controlling for marital status and employment in addition to matching variables.RESULTSCompared with never e-cigarette smokers, e-cigarette smokers had increased odds of self-reported ACOS (OR=2.27; 95% CI: 2.23–2.31), asthma (OR=1.26; 95% CI: 1.25–1.27) and COPD (OR=1.44; 95% CI: 1.42–1.46).CONCLUSIONSData from this large nationally representative sample suggest that e-cigarette use is associated with increased odds of self-reported asthma, COPD, and ACOS among never combustible cigarette smokers. The odds of ACOS were twice as high among e-cigarette users compared with never smokers of conventional cigarettes. The findings from this study suggest the need to further investigate the long-term and short-term health effects of e-cigarette use, since the age of those at risk in our study was 18–24 years.

A MATTER OF FLUX: A CASE REPORT ON ARC WELDER'S LUNG

SESSION TITLE: Medical Student/Resident Occupational and Environmental Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Occupational diseases are a major cause of individual health deterioration We present a case of occupational exposure to metal fumes resulting in Arc Welder’s Lungs (AWL). CASE PRESENTATION: A 63-year old male presented with shortness of breath and productive cough for 8 days. He was a welder for 27 years. He never smoked and was not taking any medications. He was afebrile, hypoxic at 78% O2 saturation, respiratory rate was 31, pulse of 97 and blood pressure of 172/90 mmHg. He had diffuse rhonchi most prominent in the bibasilar lung fields. Labs revealed a leukocytosis of 14.2 K/uL, normal liver and chemistry panels and a procalcitonin of 0.1 ng/mL. Chest X Ray showed perihilar and basilar multifocal consolidation.(Image A) A chest CT angiography was negative for pulmonary embolism but showed extensive bilateral focal consolidation and diffuse ground glass opacities with an enlarged main pulmonary artery.(Image B) He was started on antibiotics, steroids and required 6L of nasal cannula. Transthoracic echocardiography showed severe left ventricular hypertrophy, an ejection fraction of 70% and an estimated pulmonary artery pressure of 91 mmHg. His symptoms progressively worsened and oxygen requirements escalated. Viral panels, autoimmune serologies, amyloid workup and cultures were all negative. A right heart catheterization showed right atrial pressure of 6 mmHg, right ventricular pressure of 75/5 mmHg, pulmonary capillary wedge pressure of 10 mmHg, a cardiac index of 3.9 L/min/m2 and pulmonary vascular resistance of 5.3 WU suggesting a potential arteriopathy component in the setting of acute pulmonary inflammation. A bronchoscopy with lavage showed numerous hemosiderin laden macrophage with positive iron staining and positive oil red O stain. A transbronchial biopsy was not pursued due to potential bleeding risk in setting of pulmonary hypertension. Serum ferritin level was 2163 ng/mL. Based on occupational history and bronchoscopy findings, the patient was diagnosed with AWL. Given the acute inflammatory parenchymal process, pulse dose steroids were initiated with subsequent clinical improvement. DISCUSSION: AWL can present in different forms of lung disease.[1] Cases are usually “benign” without residual effects, however there are reports of symptomatic presentations with underlying fibrosis.[2] We describe the first welder’s lung case with an acute inhalational pneumonitis responsive to pulse dose steroids. Three months interval CT scan showed significant improvement of ground glass component with residual areas of underlying reticular and fibrotic changes in the bases, possibly suggestive of desquamative interstitial pneumonia.(Image C) CONCLUSIONS: Our case highlights the implications of occupational diseases which can be preventable and the possible variability in presentations. Physicians should be aware of AWL and include it in their differential diagnosis Reference #1: Riccelli MG, Goldoni M, Poli D, Mozzoni P, Cavallo D, Corradi M. Welding Fumes, a Risk Factor for Lung Diseases. Int J Environ Res Public Health. 2020;17(7):2552. Published 2020 Apr 8. doi:10.3390/ijerph17072552 Reference #2: M. P. Cosgrove, Pulmonary fibrosis and exposure to steel welding fume, Occupational Medicine, Volume 65, Issue 9, December 2015, Pages 706–712, https://doi.org/10.1093/occmed/kqv093 DISCLOSURES: No relevant relationships by Youssef Abouleish, source=Web Response No relevant relationships by Mit Patel, source=Web Response No relevant relationships by Anthony Quaranta, source=Web Response

Is Umbilical Cord Blood Therapy an Effective Treatment for Early Lung Injury in Growth Restriction?

Fetal growth restriction (FGR) and prematurity are often co-morbidities, and both are risk factors for lung disease. Despite advances in early delivery combined with supportive ventilation, rates of ventilation-induced lung injury (VILI) remain high. There are currently no protective treatments or interventions available that target lung morbidities associated with FGR preterm infants. Stem cell therapy, such as umbilical cord blood (UCB) cell administration, demonstrates an ability to attenuate inflammation and injury associated with VILI in preterm appropriately grown animals. However, no studies have looked at the effects of stem cell therapy in growth restricted newborns. We aimed to determine if UCB treatment could attenuate acute inflammation in the first 24 h of ventilation, comparing effects in lambs born preterm following FGR with those born preterm but appropriately grown (AG). Placental insufficiency (FGR) was induced by single umbilical artery ligation in twin-bearing ewes at 88 days gestation, with twins used as control (appropriately grown, AG). Lambs were delivered preterm at ~126 days gestation (term is 150 days) and randomized to either immediate euthanasia (unventilated controls, AGUVC and FGRUVC) or commenced on 24 h of gentle supportive ventilation (AGV and FGRV) with additional cohorts receiving UCB treatment at 1 h (AGCELLS, FGRCELLS). Lungs were collected at post-mortem for histological and biochemical examination. Ventilation caused lung injury in AG lambs, as indicated by decreased septal crests and elastin density, as well as increased inflammation. Lung injury in AG lambs was attenuated with UCB therapy. Ventilated FGR lambs also sustained lung injury, albeit with different indices compared to AG lambs; in FGR, ventilation reduced septal crest density, reduced alpha smooth muscle actin density and reduced cell proliferation. UCB treatment in ventilated FGR lambs further decreased septal crest density and increased collagen deposition, however, it increased angiogenesis as evidenced by increased vascular endothelial growth factor (VEGF) expression and vessel density. This is the first time that a cell therapy has been investigated in the lungs of growth restricted animals. We show that the uterine environment can alter the response to both secondary stress (ventilation) and therapy (UCB). This study highlights the need for further research on the potential impact of novel therapies on a growth restricted offspring.

Perspectives of Healthcare Workers, National and Regional Policy Stakeholders on the Management of Chronic Lung Disease in Five Sub-Saharan African Countries: Tale of a Vicious Cycle of Neglect

Background: Chronic lung diseases are among the top four non communicable diseases (NCDs), associated with 80% of premature mortality worldwide, debilitating health, and poor quality of life for survivors. Common risk factors for lung diseases include exposure to biomass fuels, environmental pollution, tobacco smoke, hereditary factors, and lower respiratory tract infections. Low-and-middle-income countries bear the biggest burden of chronic lung diseases, due to increasing exposures to risk factors, and weak health systems.To manage this rising threat, countries need to orient their systems towards chronic disease management, strengthen their primary healthcare systems even as they pursue universal health coverage reforms. This paper draws on the views and experiences of health systems actors to explore the current challenges to improving high quality, accessible care for chronic lung diseases.Methods: We explored the perspectives of policy stakeholders on management of chronic lung diseases in five Sub-Saharan African countries, Kenya, Malawi, Sudan, Tanzania, and Uganda. Data were collected between May 2018 and March 2019 through key informant interviews and in-depth interviews with government officials, representatives of non-governmental organizations supporting various health system functions, and healthcare workers of 36 healthcare facilities. Data were analysed using the framework approach.Findings: We identified intersecting vicious cycles of neglect of chronic lung health at both the strategic policy level and the healthcare facility level. At strategic policy level, low diagnostic capacity, weak recording and reporting systems limit the availability of reliable data on the burden of disease, which negatively affects inclusion in policy, and in turn budgetary allocations for diagnostic equipment, training, and medicines. At the service level, lack of budgetary allocations for equipment and training of staff, constrains diagnostic capacity, which, along with limited availability of appropriate medicines reduces service delivery quality and collection of appropriate data within healthcare facilities. These vicious cycles leave health systems ill equipped to respond to the rising burden of chronic lung disease, an issue that has been brought into sharp focus as countries plan for dealing with post COVID lung disease. Interpretation: 1. There is increasing recognition among policymakers that NCDs, including CLD are rising in LMICs.2. CLDs are under-diagnosed, under-reported and underfunded leading to a vicious cycle of invisibility and neglect at all levels of the health system.3. Appropriate diagnosis and CLD management require strengthening of the health systems, particularly at the primary healthcare level.Funding Statement: This research was funded by the National Institute for Health Research (NIHR (IMPALA, grant reference 16/136/35) using UK aid from the UK Government to support global health research.Declaration of Interests: None declared.Ethics Approval Statement: The Liverpool School of Tropical Medicine Ethics Committee approved these studies separately (Kenya: protocol 18-054; Uganda: protocol 18-037; Malawi: protocol M1803; Tanzania and Sudan; protocol 18-043). Additionally, each approved was by in-country committees.

Low-moderate arsenic exposure and respiratory in American Indian communities in the Strong Heart Study

BackgroundArsenic exposure through drinking water is an established lung carcinogen. Evidence on non-malignant lung outcomes is less conclusive and suggests arsenic is associated with lower lung function. Studies examining low-moderate arsenic (< 50 μg/L), the level relevant for most populations, are limited. We evaluated the association of arsenic exposure with respiratory health in American Indians from the Northern Plains, the Southern Plains and the Southwest United States, communities with environmental exposure to inorganic arsenic through drinking water.MethodsThe Strong Heart Study is a prospective study of American Indian adults. This analysis used urinary arsenic measurements at baseline (1989–1991) and spirometry at Visit 2 (1993–1995) from 2132 participants to evaluate associations of arsenic exposure with airflow obstruction, restrictive pattern, self-reported respiratory disease, and symptoms.ResultsAirflow obstruction was present in 21.5% and restrictive pattern was present in 14.4%. The odds ratio (95% confidence interval) for obstruction and restrictive patterns, based on the fixed ratio definition, comparing the 75th to 25th percentile of arsenic, was 1.17 (0.99, 1.38) and 1.27 (1.01, 1.60), respectively, after adjustments, and 1.28 (1.02, 1.60) and 1.33 (0.90, 1.50), respectively, based on the lower limit of normal definition. Arsenic was associated with lower percent predicted FEV1 and FVC, self-reported emphysema and stopping for breath.ConclusionLow-moderate arsenic exposure was positively associated with restrictive pattern, airflow obstruction, lower lung function, self-reported emphysema and stopping for breath, independent of smoking and other lung disease risk factors. Findings suggest that low-moderate arsenic exposure may contribute to restrictive lung disease.

Diagnoses from lung specimen collected through flexible bronchoscopy from patients in a tertiary hospital in Dar es Salaam Tanzania: a retrospective cross-sectional study

BackgroundFlexible bronchoscopy enables visualization of the respiratory airway mucosa from the oropharynx to third generation branching of the tracheobronchial tree. Bronchoscopic diagnoses vary from one locality to the other in accordance to the locality specific risk factors for lung diseases. This study aimed at describing diagnoses of all specimen of patients who underwent flexible bronchoscopy at Muhimbili National Hospital from January 2013 to November 2017.MethodsA retrospective hospital-based cross sectional study was conducted among 451 patients. Data was collected from archives and included both demographic and clinical variables. Descriptive statistics were used to summarize the study findings.ResultsThere was a 3 fold increase in the number of patients who underwent flexible bronchoscopy from 57 cases in 2013 to 180 cases in 2017. About 39% (174/451) of patients underwent lung biopsies while 64.5% (291/451) underwent bronchioalveolar lavage, bronchial washings or brush cytology, alone or in combination with biopsy. Generally, 64.4% (112/174) of all lung biopsies were malignant. Adenocarcinoma was the most common diagnosis seen in 33.9% (59/174). Of 76 cytological samples which were sent for bacterial culture and sensitivity, 11/76 (11.8%) were culture positive. A total of 6 (10.7%) out of 56 samples which were sent for GeneXpert MTB/RIF tested positive for M.tuberculosis.ConclusionAdenocarcinoma was the most common diagnosis. Bacterial and mycobacterial infections were among the most reported findings in cytological samples. Suspicious tuberculosis lesions during bronchoscopy made it possible to diagnose tuberculosis which was hard to diagnose before patients were sent for bronchoscopy.

Effect of Marijuana Smoking on Pulmonary Disease in HIV-Infected and Uninfected Men: A Longitudinal Cohort Study

SummaryBackgroundLung disease is a common comorbidity in people with HIV/AIDS, independent of smoking status. The effects of marijuana smoking on risk of lung disease in HIV-infected individuals are unclear.MethodsIn this prospective cohort study, we quantified lung disease risk among men enrolled in the Multicenter AIDS Cohort Study (MACS), a long-term observational cohort of HIV-infected and uninfected men who have sex with men. Eligible participants were aged ≥ 30 years with self-reported marijuana and tobacco smoking data from biannual study visits between 1996 and 2014. Pulmonary diagnoses were obtained from self-report and medical records. Analyses were performed using Cox models and Generalized Estimating Equations adjusted for tobacco smoking, CD4 T cell count, and other risk factors.Findings1630 incident pulmonary diagnoses were reported among 1352 HIV-seropositive and 1352 HIV-seronegative eligible participants matched for race and baseline age (53,794 total person-visits, median follow-up 10.5 years). 27% of HIV-infected participants reported daily or weekly marijuana smoking for one or more years in follow-up, compared to 18% of uninfected participants (median 4·0 and 4·5 years daily/weekly use, respectively). HIV-infected participants had an increased likelihood of infectious or non-infectious pulmonary diagnoses compared to uninfected participants (33·2% vs. 21·5%, and 20·6% vs. 17·2%, respectively). Among HIV-infected participants, recent marijuana smoking was associated with increased risk of infectious pulmonary diagnoses and chronic bronchitis independent of tobacco smoking and other risk factors for lung disease (hazard ratio [95% confidence interval] 1·43 [1·09–1·86], and 1·54 [1·11–2·13], respectively); these risks were additive in participants smoking both substances. There was no association between marijuana smoking and pulmonary diagnoses in HIV-uninfected participants.InterpretationIn this longitudinal study, long-term marijuana smoking was associated with lung disease independent of tobacco smoking and other risk factors in HIV-infected individuals. These findings could be used to reduce modifiable risks of lung disease in high-risk populations.FundingU.S. National Institutes of Health.

Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques.

In the era of combined antiretroviral therapy (cART), lung diseases such as chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD) are common among persons living with HIV (PLWH), particularly smokers. Although smoking is highly prevalent among PLWH, HIV may be an independent risk factor for lung diseases; however, the role of HIV and cigarette smoke (CS) and their potential interaction in the development of chronic lung diseases among PLWH has not been delineated. To investigate this interaction, cynomolgus macaques were exposed to CS and/or simian-adapted human immunodeficiency virus (SHIV) and treated with cART. The development of CB and the lung functions were evaluated following CS±SHIV treatment. The results showed that in the lung, SHIV was a strong independent risk factor for goblet cell metaplasia/hyperplasia and mucus formation, MUC5AC synthesis, loss of tight junction proteins, and increased expression of Th2 cytokines/transcription factors. In addition, SHIV and CS synergistically reduced lung function and increased extrathoracic tracheal ring thickness. Interestingly, SHIV infection generated significant numbers of HIV-gp120+ epithelial cells (HGECs) in small airways and alveoli, and their numbers doubled in CS+SHIV-infected lungs. We conclude that even with cART, SHIV independently induces CB and pro-COPD changes in the lung, and the effects are exacerbated by CS.

Seasonal fluctuation of lung function in cystic fibrosis: A national register-based study in two northern European populations

BackgroundMany risk factors for lung disease in cystic fibrosis (CF) display a seasonal pattern yet it is unclear whether this is reflected in seasonal fluctuations in lung function. MethodsWe conducted a longitudinal study using CF registries in Denmark and the UK. 471 individuals with a median of 104 FEV1 measurements per person and 7586 individuals with a median of nine FEV1 measures per person were included from Denmark and the UK respectively. We estimated the effect of seasonality on percent predicted FEV1 trajectories using mixed effects models whilst adjusting for clinically important covariates. ResultsWe found no significant cyclical seasonal variation in lung function in either country. The maximum variation in percent predicted FEV1 around the yearly average was estimated to be 0.1 percentage points (95%CI 0 to 0.21) and 0.14 percentage points (95%CI 0 to 0.29) in Denmark and the UK, respectively. When considering possible step-like changes between the four seasons, we found that lung function was higher in spring compared to winter in the UK (0.34 percentage points, 95%CI 0.1 to 0.59) though the difference was not of clinical significance. ConclusionIn both the UK and Denmark there may be small seasonal changes in lung function but this effect is not of clinical importance.

Questionnaires for Lung Health in Africa across the Life Course.

Respiratory infections remain a leading cause of morbidity and mortality in many low and middle-income countries but non-communicable disease rates are rising fast. Prevalence studies have been primarily symptom-focused, with tools developed in countries in the Global North such as the United States and the United Kingdom. Systematic study in sub-Saharan African populations is necessary to accurately reflect disease risk factors present in these populations. We present tools for such studies, developed as part of the International Multidisciplinary Programme to Address Lung Health and TB in Africa (‘IMPALA’), which includes lay representatives. At a preliminary meeting, the adequacy and suitability of existing tools was discussed and a new questionnaire set proposed. Individual questionnaires were developed, and an expert panel considered content and criterion validity. Questionnaires underwent a cross-cultural adaptation process, incorporating translation and contextual ‘sense-checking’, through the use of pre-established lay focus groups in Malawi, before consensus-approval by project collaborators. The complete set of research questionnaires, providing information on lung health symptoms and a relevant range of potential risk factors for lung disease, is now available online. In developing the tools, cultural and contextual insights were important, as were translational considerations. The process benefitted from a foundation in expert knowledge, starting with validated tools and internationally respected research groups, and from a coordinated collaborative approach. We present and discuss a newly devised, contextually appropriate set of questionnaires for non-communicable lung disease research in Africa that are now available in open access for all to use.

SGK1 inhibits PM2.5-induced apoptosis and oxidative stress in human lung alveolar epithelial A549 cells

Emerging evidence demonstrated that particulate matter 2.5 (PM2.5) is an important environmental risk factor for lung diseases. Serum- and glucocorticoid-inducible kinase 1(SGK1) was reported to be a crucial factor for cell survival. However, the role of SGK1 in PM2.5-induced cell injury is still unclear. In this work, we firstly found that the expression of SGK1 was decreased in PM2.5-treated human lung alveolar epithelial (A549) cells by western blot. In addition, overexpression of SGK1 significantly attenuated A549 cell apoptosis and reduced the reactive oxygen species (ROS) generation induced by PM2.5. Moreover, we found that PM2.5 exposure significantly promoted the ERK1/2 activation and inhibited the AKT activation, whereas overexpression of SGK1 could reverse that. Finally, the results of the rescue experiment showed that MK2206 (AKT inhibitor) could rescue the impact of SGK1 on A549 cell apoptosis, while PD98059 (ERK1/2 inhibitor) could not further aggravate the impact. Taken together, our results suggest that SGK1 inhibits PM2.5-induced cell apoptosis and ROS generation via ERK1/2 and AKT signaling pathway in human lung alveolar epithelial A549 cells.

Modeling the Effect of the Aryl Hydrocarbon Receptor on Transplant Immunity.

BackgroundExposure to pollutants through inhalation is a risk factor for lung diseases including cancer, asthma, and lung transplant rejection, but knowledge of the effects of inhaled pollutants on pathologies outside of the lung is limited.MethodsUsing the minor-mismatched model of male C57BL/6J (B6) to female B6 skin grafts, recipient mice were treated with an inhaled urban dust particle sample every 3 days before and after grafting. Graft survival time was determined, and analysis of the resulting immune response was performed at time before rejection.ResultsSignificant prolongation of male skin grafts occurred in recipient female mice treated with urban dust particles compared with controls and was found to be dependent on aryl hydrocarbon receptor (AHR) expression in the recipient mouse. T cell responses to the male histocompatibility antigen (H-Y) Dby were not altered by exposure to pollutants. A reduction in the frequency of IFNγ-producing CD4 T cells infiltrating the graft on day 7 posttransplant was observed. Flow cytometry analysis revealed that AHR expression is upregulated in IFNγ-producing CD4 T cells during immune responses in vitro and in vivo.ConclusionsSurprisingly, inhalation of a pollutant standard was found to prolong graft survival in a minor-mismatched skin graft model in an AHR-dependent manner. One possible mechanism may be an effect on IFNγ-producing CD4 T cells responding to donor antigen. The increased expression of AHR in this CD4 T cell subset suggests that AHR ligands within the particulate matter may be directly affecting the type 1 T helper cell response in this model.