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Arthritis & Rheumatology (Hoboken, N.J.) Nov 2021To investigate the independent relationship of rheumatoid arthritis (RA) to the type and severity of pulmonary patterns on spirometry compared to the pulmonary patterns...
OBJECTIVE
To investigate the independent relationship of rheumatoid arthritis (RA) to the type and severity of pulmonary patterns on spirometry compared to the pulmonary patterns in general population controls.
METHODS
In this cross-sectional study, we investigated the association of RA with pulmonary function measures on spirometry among subjects in the UK Biobank who underwent spirometry for research purposes. RA cases were identified based on self-report and current disease-modifying antirheumatic drug/glucocorticoid use. Controls were subjects without RA from the general population. Outcome measures included continuous forced expiratory volume in 1 second percent predicted (FEV %) and forced vital capacity percent predicted (FVC%), type of spirometric pattern (restrictive or obstructive), and severity of the restrictive or obstructive pattern. We used multivariable regression to estimate the effects in RA cases compared to the effects in controls, adjusting for age, sex, body mass index, and smoking status/pack-years.
RESULTS
Among 350,776 analyzed subjects who underwent spirometry (mean age 56.3 years; 55.8% female; 45.5% ever smokers), we identified 2,008 cases of treated RA. In multivariable analyses, RA was associated with lower FEV % (β = -2.93 [95% confidence interval (95% CI) -3.63, -2.24]), FVC% (β = -2.08 [95% CI -2.72, -1.45]), and FEV /FVC (β = -0.008 [95% CI -0.010, -0.005]) compared to controls. RA was additionally associated with restrictive patterns (odds ratio [OR] 1.36 [95% CI 1.21, 1.52]) and obstructive patterns (OR 1.21 [95% CI 1.07, 1.37]) independent of confounders, and was most strongly associated with severe restrictive and obstructive patterns.
CONCLUSION
RA is associated with increased odds of restrictive and obstructive patterns, and this relationship is not explained by confounders, including smoking status. In addition to restrictive lung disease, clinicians should also be aware that airway obstruction may be a pulmonary manifestation of RA.
Topics: Adult; Aged; Arthritis, Rheumatoid; Biological Specimen Banks; Cross-Sectional Studies; Female; Humans; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Spirometry; United Kingdom
PubMed: 33982900
DOI: 10.1002/art.41791 -
Nature Communications May 2023Prevention and management of chronic lung diseases (asthma, lung cancer, etc.) are of great importance. While tests are available for reliable diagnosis, accurate...
Prevention and management of chronic lung diseases (asthma, lung cancer, etc.) are of great importance. While tests are available for reliable diagnosis, accurate identification of those who will develop severe morbidity/mortality is currently limited. Here, we developed a deep learning model, CXR Lung-Risk, to predict the risk of lung disease mortality from a chest x-ray. The model was trained using 147,497 x-ray images of 40,643 individuals and tested in three independent cohorts comprising 15,976 individuals. We found that CXR Lung-Risk showed a graded association with lung disease mortality after adjustment for risk factors, including age, smoking, and radiologic findings (Hazard ratios up to 11.86 [8.64-16.27]; p < 0.001). Adding CXR Lung-Risk to a multivariable model improved estimates of lung disease mortality in all cohorts. Our results demonstrate that deep learning can identify individuals at risk of lung disease mortality on easily obtainable x-rays, which may improve personalized prevention and treatment strategies.
Topics: Humans; Deep Learning; Radiography, Thoracic; Lung; Lung Diseases; Thorax
PubMed: 37193717
DOI: 10.1038/s41467-023-37758-5 -
Current Opinion in Rheumatology Nov 2019Systemic sclerosis (SSc) is a heterogeneous disease with a variable disease course. Interstitial lung disease (ILD) is one of the leading causes of morbidity and... (Review)
Review
PURPOSE OF REVIEW
Systemic sclerosis (SSc) is a heterogeneous disease with a variable disease course. Interstitial lung disease (ILD) is one of the leading causes of morbidity and mortality in patients with SSc. The present review highlights recent advances in the classification, diagnosis, and early detection of SSc-associated ILD (SSc-ILD).
RECENT FINDINGS
Risk stratification through measurement of disease extent on high-resolution computed tomography (HRCT) of the chest, longitudinal declines in pulmonary function tests (PFTs), and mortality prediction models have formed the basis for classifying clinically significant ILD. HRCT may be preferred over PFTs for screening, as PFTs lack sensitivity and have a high false-negative rate. Novel imaging modalities and biomarkers hold promise as adjunct methods for assessing the presence and severity of SSc-ILD, and predicting risk for progressive disease. Further validation is required prior to their use in clinical settings.
SUMMARY
Classification of SSc-ILD has shifted to a personalized approach that considers an individual patient's probability of progressive disease through identification of risk factors, measurement of disease extent on HRCT, longitudinal declines in PFTs, and mortality prediction models. There remains an unmet need to develop screening guidelines for SSc-ILD.
Topics: Early Diagnosis; Humans; Lung; Lung Diseases, Interstitial; Mass Screening; Respiratory Function Tests; Risk Factors; Scleroderma, Systemic; Tomography, X-Ray Computed
PubMed: 31415029
DOI: 10.1097/BOR.0000000000000660 -
Scientific Reports Jul 2020Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by interstitial remodeling and pulmonary dysfunction. The etiology of IPF is not completely...
Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by interstitial remodeling and pulmonary dysfunction. The etiology of IPF is not completely understood but involves pathologic inflammation and subsequent failure to resolve fibrosis in response to epithelial injury. Treatments for IPF are limited to anti-inflammatory and immunomodulatory agents, which are only partially effective. Prostaglandin E2 (PGE2) disrupts TGFβ signaling and suppresses myofibroblast differentiation, however practical strategies to raise tissue PGE2 during IPF have been limited. We previously described the discovery of a small molecule, (+)SW033291, that binds with high affinity to the PGE2-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and increases PGE2 levels. Here we evaluated pulmonary 15-PGDH expression and activity and tested whether pharmacologic 15-PGDH inhibition (PGDHi) is protective in a mouse model of bleomycin-induced pulmonary fibrosis (PF). Long-term PGDHi was well-tolerated, reduced the severity of pulmonary fibrotic lesions and extracellular matrix remodeling, and improved pulmonary function in bleomycin-treated mice. Moreover, PGDHi attenuated both acute inflammation and weight loss, and decreased mortality. Endothelial cells and macrophages are likely targets as these cell types highly expressed 15-PGDH. In conclusion, PGDHi ameliorates inflammatory pathology and fibrosis in murine PF, and may have clinical utility to treat human disease.
Topics: Animals; Anti-Inflammatory Agents; Bleomycin; Body Weight; Dinoprostone; Disease Models, Animal; Endothelial Cells; Enzyme Inhibitors; Extracellular Matrix; Female; Gene Expression; Humans; Hydroxyprostaglandin Dehydrogenases; Idiopathic Pulmonary Fibrosis; Inflammation; Lung; Macrophages; Mice; Mice, Inbred C57BL; Molecular Targeted Therapy; Pyridines; Respiratory Function Tests; Survival Analysis; Thiophenes
PubMed: 32669620
DOI: 10.1038/s41598-020-68336-0 -
Organic Letters Jun 2020The clinically approved Fondaparinux (Arixtra) has been used for the treatment of deep vein thrombosis and acute pulmonary embolism since 2002 and is considered to be...
The clinically approved Fondaparinux (Arixtra) has been used for the treatment of deep vein thrombosis and acute pulmonary embolism since 2002 and is considered to be better than the low-molecular weight heparin in terms of anticoagulation response, duration of action, and biosafety. However, the synthetic methods previously developed for its manufacture are relatively complicated, thus restricting its extensive use. We report here a potentially scalable and programmable one-pot synthesis of Fondaparinux using the [1,2,2] strategy and designed thioglycosides with well-defined reactivity as building blocks.
Topics: Anticoagulants; Chemistry Techniques, Synthetic; Fondaparinux; Heparin; Molecular Weight
PubMed: 32496799
DOI: 10.1021/acs.orglett.0c01386 -
International Journal of Chronic... 2022Previous studies have demonstrated that there is a certain correlation between emphysema and changes in pulmonary small blood vessels in patients with chronic...
BACKGROUND
Previous studies have demonstrated that there is a certain correlation between emphysema and changes in pulmonary small blood vessels in patients with chronic obstructive pulmonary disease (COPD), but most of them were limited to the investigation of the inspiratory phase. The emphysema indicators need to be further optimized. Based on the parametric response mapping (PRM) method, this study aimed to investigate the effect of emphysema and functional small airway disease on intrapulmonary vascular volume (IPVV).
METHODS
This retrospective study enrolled 63 healthy subjects and 47 COPD patients, who underwent both inspiratory and expiratory CT scans of the chest and pulmonary function tests (PFTs). Inspiratory and expiratory IPVV were measured by using an automatic pulmonary vessels integration segmentation approach, the ratio of emphysema volume (Emph%), functional small airway disease volume (fsAD%), and normal areas volume (Normal%) were quantified by the PRM method for biphasic CT scans. The participants were grouped according to PFTs. Analysis of variance (ANOVA) and Kruskal-Wallis H-test were used to analyze the differences in indicators between different groups. Then, Spearman's rank correlation coefficients were used to analyze the correlation between Emph%, fsAD%, Normal%, PFTs, and IPVV. Finally, multiple linear regression was applied to analyze the effects of Emph% and fsAD% on IPVV.
RESULTS
Differences were found in age, body mass index (BMI), smoking index, FEV1%, FEV1/forced vital capacity (FVC), expiratory IPVV, IPVV relative value, IPVV difference value, Emph%, fsAD%, and Normal% between the groups (<0.05). A strong correlation was established between the outcomes of PFTs and quantitative CT indexes. Finally, the effect of Emph% was more significant than that of fsAD% on expiratory IPVV, IPVV difference value, and IPVV relative value.
CONCLUSION
IPVV may have a potential value in assessing COPD severity and is significantly affected by emphysema.
Topics: Asthma; Emphysema; Forced Expiratory Volume; Humans; Lung; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Retrospective Studies
PubMed: 36045693
DOI: 10.2147/COPD.S368974 -
Particle and Fibre Toxicology Jul 2021Multi-walled carbon nanotubes (MWCNT) have received attention due to extraordinary properties, resulting in concerns for occupational health and safety. Costs and...
BACKGROUND
Multi-walled carbon nanotubes (MWCNT) have received attention due to extraordinary properties, resulting in concerns for occupational health and safety. Costs and ethical concerns of animal testing drive a need for in vitro models with predictive power in respiratory toxicity. The aim of this study was to assess pro-inflammatory response (Interleukin-8 expression, IL-8) and genotoxicity (DNA strand breaks) caused by MWCNT with different physicochemical properties in different pulmonary cell models and correlate these to previously published in vivo data. Seven MWCNT were selected; two long/thick (NRCWE-006/Mitsui-7 and NM-401), two short/thin (NM-400 and NM-403), a pristine (NRCWE-040) and two surface modified; hydroxylated (NRCWE-041) and carboxylated (NRCWE-042). Carbon black Printex90 (CB) was included as benchmark material. Human alveolar epithelial cells (A549) and monocyte-derived macrophages (THP-1a) were exposed to nanomaterials (NM) in submerged conditions, and two materials (NM-400 and NM-401) in co-cultures of A549/THP-1a and lung fibroblasts (WI-38) in an air-liquid interface (ALI) system. Effective doses were quantified by thermo-gravimetric-mass spectrometry analysis (TGA-MS). To compare genotoxicity in vitro and in vivo, we developed a scoring system based on a categorization of effects into standard deviation (SD) units (< 1, 1, 2, 3 or 4 standard deviation increases) for the increasing genotoxicity.
RESULTS
Effective doses were shown to be 25 to 53%, and 21 to 57% of the doses administered to A549 and THP-1a, respectively. In submerged conditions (A549 and THP-1a cells), all NM induced dose-dependent IL-8 expression. NM-401 and NRCWE-006 caused the strongest pro-inflammatory response. In the ALI-exposed co-culture, only NM-401 caused increased IL-8 expression, and no DNA strand breaks were observed. Strong correlations were found between in vitro and in vivo inflammation when doses were normalized by surface area (also proxy for diameter and length). Significantly increased DNA damage was found for all MWCNT in THP-1a cells, and for short MWCNT in A549 cells. A concordance in genotoxicity of 83% was obtained between THP-1a cells and broncho-alveolar lavaged (BAL) cells.
CONCLUSION
This study shows correlations of pro-inflammatory potential in A549 and THP-1a cells with neutrophil influx in mice, and concordance in genotoxic response between THP-1a cells and BAL cells, for seven MWCNT.
Topics: A549 Cells; Alveolar Epithelial Cells; Animals; DNA Damage; Humans; Lung; Mice; Nanotubes, Carbon
PubMed: 34301283
DOI: 10.1186/s12989-021-00413-2 -
Journal of Acquired Immune Deficiency... Aug 2021People with HIV (PWH) experience chronic pain and respiratory symptoms, which are closely related in the general population. Pain may affect the impaired pulmonary...
BACKGROUND
People with HIV (PWH) experience chronic pain and respiratory symptoms, which are closely related in the general population. Pain may affect the impaired pulmonary function seen in PWH beyond its association with HIV alone. Our objective was to investigate the relationship of pain severity to pulmonary function, respiratory symptoms, and sleep disturbance in PWH.
SETTING
Study sites included the University of Pittsburgh, University of California San Francisco, and University of Washington.
METHODS
Pain, dyspnea, and sleep were assessed using the Brief Chronic Pain Questionnaire, St. George's Respiratory Questionnaire, and Pittsburgh Sleep Quality Index. Participants performed prebronchodilator and postbronchodilator spirometry and 6-minute walk test. Associations between pain severity, lung function, dyspnea, and sleep were assessed with bivariate and multiple quantile regression analysis adjusted for age, sex, race, body mass index, and smoking status.
RESULTS
Of 159 PWH, the median age was 56 years with 30.8% women. Two-thirds experienced pain in the past week, with 40.3% reporting chronic pain. Pain severity was higher with female sex (P = 0.038), non-White race (P = 0.005), current smoking (P = 0.003), and lower CD4+ count (P = 0.035). In adjusted analysis, higher pain severity was correlated with reduced postbronchodilator forced expiratory volume in 1 second %predicted (P = 0.008), reduced postbronchodilator forced vital capacity %predicted (P = 0.019), and chronic obstructive pulmonary disease (P = 0.032). Greater pain severity was strongly associated with a higher St. George's Respiratory Questionnaire score (P < 0.001) and sleep disturbance (P < 0.001).
CONCLUSIONS
In PWH, pain is common and associated with airflow obstruction, dyspnea, and sleep disturbance. Future studies assessing pain severity and pulmonary function over time could clarify the direction of this association and the impact on quality of life.
Topics: Adult; Female; HIV Infections; Humans; Lung; Male; Middle Aged; Pain; Respiratory Function Tests
PubMed: 33871410
DOI: 10.1097/QAI.0000000000002696 -
Medicina (Kaunas, Lithuania) Jul 2022: The estimation of lung function impairment after pulmonary lobectomy for primary non-small cell lung cancer (NSCLC) has been of great interest since the reduction of...
: The estimation of lung function impairment after pulmonary lobectomy for primary non-small cell lung cancer (NSCLC) has been of great interest since the reduction of respiratory function might severely affect a patient's quality of life. The perioperative factors that may have an influence on widening the gap between the postoperative measured lung function and predicted postoperative lung function were our greatest concern. We aimed to analyze the perioperative patient factors that may influence postoperative lung function in patients undergoing pulmonary lobectomy. : A retrospective study was conducted using the medical records of 199 patients who underwent lobectomy for lung cancer between July 2017 and May 2020. After comparing the achieved postoperative forced expiratory volume in 1 s (FEV1) and predicted postoperative (ppo) FEV1, patients were divided into two groups: group A ( = 127), who had preserved pulmonary lung function; and group B ( = 72), who had decreased pulmonary lung function. Primary endpoints included location of pulmonary resection, preoperative performance status, body mass index (BMI) on admission, total muscle area, and muscle index. In group A, the proportion of normal weighted patients was significantly higher than that in group B (67.7% vs. 47.2%, = 0.003). Conversely, the proportion of overweight patients was significantly higher in group B than in group A (47.2% vs. 28.3%, = 0.003). Group B had a significantly high incidence of upper lobe resection ( = 0.012). The mean total muscle area in group A was higher than that in group B, but the difference was not statistically significant. : A greater decrease in postoperative lung function than in ppo FEV1 was associated with BMI and the location of pulmonary resection in patients who underwent lobectomy. Postoperative physiologic changes due to high BMI and the resection of upper lobes need to be discussed to prevent postoperative morbidities.
Topics: Carcinoma, Non-Small-Cell Lung; Disease Progression; Humans; Lung; Lung Neoplasms; Pneumonectomy; Quality of Life; Retrospective Studies
PubMed: 36013488
DOI: 10.3390/medicina58081021 -
JCI Insight May 2023The pathogenesis of the marked pulmonary microvasculature injury, a distinguishing feature of COVID-19 acute respiratory distress syndrome (COVID-ARDS), remains unclear....
The pathogenesis of the marked pulmonary microvasculature injury, a distinguishing feature of COVID-19 acute respiratory distress syndrome (COVID-ARDS), remains unclear. Implicated in the pathophysiology of diverse diseases characterized by endothelial damage, including ARDS and ischemic cardiovascular disease, ceramide and in particular palmitoyl ceramide (C16:0-ceramide) may be involved in the microvascular injury in COVID-19. Using deidentified plasma and lung samples from COVID-19 patients, ceramide profiling by mass spectrometry was performed. Compared with healthy individuals, a specific 3-fold C16:0-ceramide elevation in COVID-19 patient plasma was identified. Compared with age-matched controls, autopsied lungs of individuals succumbing to COVID-ARDS displayed a massive 9-fold C16:0-ceramide elevation and exhibited a previously unrecognized microvascular ceramide-staining pattern and markedly enhanced apoptosis. In COVID-19 plasma and lungs, the C16-ceramide/C24-ceramide ratios were increased and reversed, respectively, consistent with increased risk of vascular injury. Indeed, exposure of primary human lung microvascular endothelial cell monolayers to C16:0-ceramide-rich plasma lipid extracts from COVID-19, but not healthy, individuals led to a significant decrease in endothelial barrier function. This effect was phenocopied by spiking healthy plasma lipid extracts with synthetic C16:0-ceramide and was inhibited by treatment with ceramide-neutralizing monoclonal antibody or single-chain variable fragment. These results indicate that C16:0-ceramide may be implicated in the vascular injury associated with COVID-19.
Topics: Humans; Vascular System Injuries; COVID-19; Ceramides; Lung; Respiratory Distress Syndrome
PubMed: 37212278
DOI: 10.1172/jci.insight.156104