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Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF
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Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pulmonology".

Deadline for manuscript submissions: closed (20 November 2018) | Viewed by 155409

Special Issue Editor

Dr. Nazia Chaudhuri

E-Mail Website1 Website2
Guest Editor
North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
Interests: Interstitial Lung Disease (ILD); diagnosis; management; idiopathic pulmonary fibrosis; sarcoidosis; hypersensitivity pneumonitis; drug-induced toxicity; drug-induced ILDs (TRISTAN)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lung diseases are amongst the leading causes of mortality world-wide, with lung infections, lung cancer and Chronic Obstructive Pulmonary Disease (COPD) being in the top 10 causes of death in 2008. One sixth of total deaths are attributed to lung disease, accounting for over 9.5 million deaths world-wide. The burden of lung disease is evident and drives the continued quest from patients, physicians and researchers to improve patient outcomes through the development of optimal services and novel therapies that can impact on disease pathogenesis, trajectory and patient outcomes. The present Special Issue on lung diseases aims to inform the reader of the cutting edge scientific and clinical advances in all aspects of lung diseases over the past decade.

Dr. Nazia Chaudhuri
Guest Editor

Manuscript Submission Information

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Keywords

  • Diagnosis
  • Treatment
  • Mortality
  • COPD
  • Bronchiectasis
  • Asthma
  • Idiopathic Pulmonary Fibrosis
  • Cystic Fibrosis
  • Lung Infection

Published Papers (18 papers)

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Editorial

Jump to: Research, Review

2 pages, 137 KiB  
Editorial
Comment from the Editor of the Special Issue: “Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF”
by Nazia Chaudhuri
J. Clin. Med. 2019, 8(12), 2060; https://doi.org/10.3390/jcm8122060 - 23 Nov 2019
Viewed by 1914
Abstract
This Special Issue on lung diseases is aimed at giving emergent researchers and clinicians an important forum to share their original research and expert reviews on key topics within respiratory diseases. This Special Issue will be of interest to general physicians and respiratory [...] Read more.
This Special Issue on lung diseases is aimed at giving emergent researchers and clinicians an important forum to share their original research and expert reviews on key topics within respiratory diseases. This Special Issue will be of interest to general physicians and respiratory specialist and will equip the reader with up-to-date knowledge on a wide array of lung diseases, including interstitial lung diseases, COPD, and Asthma. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)

Research

Jump to: Editorial, Review

17 pages, 4005 KiB  
Article
Gene Expression Changes Associated with Nintedanib Treatment in Idiopathic Pulmonary Fibrosis Fibroblasts: A Next-Generation Sequencing and Bioinformatics Study
by Chau-Chyun Sheu, Wei-An Chang, Ming-Ju Tsai, Ssu-Hui Liao, Inn-Wen Chong and Po-Lin Kuo
J. Clin. Med. 2019, 8(3), 308; https://doi.org/10.3390/jcm8030308 - 05 Mar 2019
Cited by 19 | Viewed by 7525
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease. Therapeutic options for IPF remain limited. Nintedanib, a tyrosine kinase inhibitor approved for IPF treatment, is known to inhibit fibroblasts proliferation, migration and transformation to myofibroblasts. However, how nintedanib changes [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease. Therapeutic options for IPF remain limited. Nintedanib, a tyrosine kinase inhibitor approved for IPF treatment, is known to inhibit fibroblasts proliferation, migration and transformation to myofibroblasts. However, how nintedanib changes gene regulations in IPF has never been systematically investigated. We conducted a next-generation sequencing and bioinformatics study to evaluate the changes of mRNA and miRNA profiles in IPF fibroblasts treated with 2 µM and 4 µM nintedanib, compared to those without treatment. We identified 157 upregulated and 151 downregulated genes and used STRING and DAVID databases for analysis of protein–protein interactions, biological pathways, and molecular functions. We found strong protein–protein interactions within these dysregulated genes, mostly involved in the pathways of cell cycle and mitotic cell cycle. We also discovered 13 potential miRNA–mRNA interactions associated with nintedanib treatment. After validation using miRDB, TargetScan, and RT-qPCR, we identified 4 downregulated genes (DDX11, E2F1, NPTX1, and PLXNA4) which might be repressed by the upregulated hsa-miR-486-3p. According to the proposed functions of DDX11, E2F1, and PLXNA4 reported in previous studies, these gene expression changes together might contribute to decreased proliferation of fibroblasts and decreased angiogenesis in the microenvironment of IPF. Our findings need further studies to confirm. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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11 pages, 2065 KiB  
Article
Comprehensive Lung Function Assessment Does not Allow to Infer Response to Pulmonary Rehabilitation in Patients with COPD
by Ingrid M. L. Augustin, Emiel F. M. Wouters, Sarah Houben-Wilke, Swetlana Gaffron, Daisy J. A. Janssen, Frits M. E. Franssen and Martijn A. Spruit
J. Clin. Med. 2019, 8(1), 27; https://doi.org/10.3390/jcm8010027 - 27 Dec 2018
Cited by 19 | Viewed by 4755
Abstract
The degree of lung function is frequently used as referral criterion for pulmonary rehabilitation. The efficacy of pulmonary rehabilitation was assessed in 518 chronic obstructive pulmonary disease (COPD) patients, after clustering based on a comprehensive pre-rehabilitation lung function assessment. Mean improvements in dyspnea, [...] Read more.
The degree of lung function is frequently used as referral criterion for pulmonary rehabilitation. The efficacy of pulmonary rehabilitation was assessed in 518 chronic obstructive pulmonary disease (COPD) patients, after clustering based on a comprehensive pre-rehabilitation lung function assessment. Mean improvements in dyspnea, exercise performance, health status, mood status and problematic activities of daily life after pulmonary rehabilitation were mostly comparable between the seven clusters, despite significant differences in the degree of lung function. The current study demonstrates no significant relationship between the seven lung-function-based clusters and response to pulmonary rehabilitation. Therefore, baseline lung function cannot be used to identify those who will respond well to pulmonary rehabilitation, and moreover, cannot be used as a criterion for referral to pulmonary rehabilitation in patients with COPD. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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11 pages, 2579 KiB  
Article
Effects of Corticosteroid Treatment and Antigen Avoidance in a Large Hypersensitivity Pneumonitis Cohort: A Single-Centre Cohort Study
by Laurens J. De Sadeleer, Frederik Hermans, Els De Dycker, Jonas Yserbyt, Johny A. Verschakelen, Eric K. Verbeken, Geert M. Verleden and Wim A. Wuyts
J. Clin. Med. 2019, 8(1), 14; https://doi.org/10.3390/jcm8010014 - 21 Dec 2018
Cited by 85 | Viewed by 5511
Abstract
Background: Although the third most frequent interstitial lung disease, hypersensitivity pneumonitis (HP) remains an enigmatic disease without clear diagnostic and therapeutic guidelines. We assessed the effect of the commonly used therapeutic interventions (i.e. exposure avoidance and corticosteroid treatment) in an HP cohort. Methods: [...] Read more.
Background: Although the third most frequent interstitial lung disease, hypersensitivity pneumonitis (HP) remains an enigmatic disease without clear diagnostic and therapeutic guidelines. We assessed the effect of the commonly used therapeutic interventions (i.e. exposure avoidance and corticosteroid treatment) in an HP cohort. Methods: We collected clinical data of all HP patients followed at our centre between January 1, 2005, and December 31, 2016. HP patients were stratified according to the presence of fibrosis on chest CT. Survival was analysed using the multivariate Cox proportional hazards model. Forced vital capacity (percent predicted, FVC%) and diffusing capacity of the lung for carbon monoxide (percent predicted, DLCO%) evolution were analysed using linear mixed-effect models. Results: Two hundred and two HP patients were identified: 93 non-fibrotic HP (nfHP) and 109 fibrotic HP (fHP), experiencing a monthly FVC% decline before treatment of 0.93% and 0.56%, respectively. While nfHP had an excellent survival, fHP patients experienced a median survival of 9.2 years. Corticosteroid treatment and exposure avoidance did not result in survival differences. Although nfHP patients showed FVC% and DLCO% increase after corticosteroid initiation, no therapeutic effect was seen in fHP patients. FVC% and DLCO% increased in nfHP patients after exposure avoidance, while a positive numerical trend was seen for FVC% after exposure avoidance in fHP patients (p = 0.15). Conclusions: nfHP patients experienced an excellent survival with good therapeutic effect on pulmonary function tests with both corticosteroid initiation as well as antigen avoidance. In contrast, fHP patients experienced a dismal prognosis (median survival of 9.2 years) without any therapeutic effect of corticosteroid treatment. Whether antigen avoidance is useful in fHP patients is still unclear. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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11 pages, 537 KiB  
Article
Tarsal Tunnel Mechanosensitivity Is Increased in Patients with Asthma: A Case-Control Study
by César Calvo-Lobo, Roi Painceira-Villar, Daniel López-López, Vanesa García-Paz, Ricardo Becerro-de-Bengoa-Vallejo, Marta Elena Losa-Iglesias and Patricia Palomo-López
J. Clin. Med. 2018, 7(12), 541; https://doi.org/10.3390/jcm7120541 - 12 Dec 2018
Cited by 8 | Viewed by 3769
Abstract
Background: Based on changes in lung function and musculoskeletal disorders in patients with asthma, this study aimed to compare the tarsal tunnel and fibular bone pressure pain thresholds (PPTs) of patients with asthma and healthy matched-paired controls. Methods: A case-control study was performed. [...] Read more.
Background: Based on changes in lung function and musculoskeletal disorders in patients with asthma, this study aimed to compare the tarsal tunnel and fibular bone pressure pain thresholds (PPTs) of patients with asthma and healthy matched-paired controls. Methods: A case-control study was performed. One hundred participants were recruited: 50 asthma patients and 50 healthy matched-paired controls. Bilaterally, tarsal tunnel and fibula bone PPTs were registered. Results: Statistically significant differences (p < 0.01) were shown bilaterally for tarsal tunnel PPT. With the exception of fibula PPT (p > 0.05), asthma patients presented less tarsal tunnel PPT than healthy participants. Statistically significant differences (p < 0.05) were shown for two linear regression prediction models of the right (R2 = 0.279) and left (R2 = 0.249) tarsal tunnels PPTs as dependent variables, and based on sex, group, contralateral tarsal tunnel PPT and ipsilateral fibula PPT as independent variables. Conclusions: The study findings showed that a bilateral tarsal tunnel mechanosensitivity increase is exhibited in patients diagnosed with asthma. The presence of asthma may bilaterally predict the PPT of tarsal tunnel. These findings may suggest the presence of central sensitization in asthma patients, which could clinically predispose them to musculoskeletal disorders, such as tarsal tunnel syndrome. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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12 pages, 508 KiB  
Article
Small Airway Disease in Pulmonary Hypertension—Additional Diagnostic Value of Multiple Breath Washout and Impulse Oscillometry
by Frederik Trinkmann, Joshua Gawlitza, Monique Künstler, Julia Schäfer, Michele Schroeter, Julia D. Michels, Ksenija Stach, Christina Dösch, Joachim Saur, Martin Borggrefe and Ibrahim Akin
J. Clin. Med. 2018, 7(12), 532; https://doi.org/10.3390/jcm7120532 - 09 Dec 2018
Cited by 9 | Viewed by 3313
Abstract
Airways obstruction is frequent in patients with pulmonary hypertension (PH). Small airway disease (SAD) was identified as a major contributor to resistance and symptoms. However, it is easily missed using current diagnostic approaches. We aimed to evaluate more elaborate diagnostic tests such as [...] Read more.
Airways obstruction is frequent in patients with pulmonary hypertension (PH). Small airway disease (SAD) was identified as a major contributor to resistance and symptoms. However, it is easily missed using current diagnostic approaches. We aimed to evaluate more elaborate diagnostic tests such as impulse oscillometry (IOS) and SF6-multiple-breath-washout (MBW) for the assessment of SAD in PH. Twenty-five PH patients undergoing body-plethysmography, IOS and MBW testing were prospectively included and equally matched to pulmonary healthy and non-healthy controls. Lung clearance index (LCI) and acinar ventilation heterogeneity (Sacin) differed significantly between PH, healthy and non-healthy controls. Likewise, differences were found for all IOS parameters between PH and healthy, but not non-healthy controls. Transfer factor corrected for ventilated alveolar volume (TLCO/VA), frequency dependency of resistance (D5-20), resonance frequency (Fres) and Sacin allowed complete differentiation between PH and healthy controls (AUC (area under the curve) = 1.0). Likewise, PH patients were separated from non-healthy controls (AUC 0.762) by D5-20, LCI and conductive ventilation heterogeneity (Scond). Maximal expiratory flow (MEF) values were not associated with additional diagnostic values. MBW and IOS are feasible in PH patients both providing additional information. This can be used to discriminate PH from healthy and non-healthy controls. Therefore, further research targeting SAD in PH and evaluation of therapeutic implications is justified. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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11 pages, 845 KiB  
Article
Mucolytic Agents and Statins Use is Associated with a Lower Risk of Acute Exacerbations in Patients with Bronchiectasis-Chronic Obstructive Pulmonary Disease Overlap
by Vincent Yi-Fong Su, Diahn-Warng Perng, Ting-Chun Chou, Yueh-Ching Chou, Yuh-Lih Chang, Chia-Chen Hsu, Chia-Lin Chou, Hsin-Chen Lee, Tzeng-Ji Chen and Po-Wei Hu
J. Clin. Med. 2018, 7(12), 517; https://doi.org/10.3390/jcm7120517 - 04 Dec 2018
Cited by 9 | Viewed by 4174
Abstract
Background: Bronchiectasis-chronic obstructive pulmonary disease (COPD) overlap (BCO) is a neglected area of trials, and it is not covered by guidelines for clinical practice. Methods: Using the National Health Insurance Research Database of Taiwan, COPD patients with or without bronchiectasis from 2000 to [...] Read more.
Background: Bronchiectasis-chronic obstructive pulmonary disease (COPD) overlap (BCO) is a neglected area of trials, and it is not covered by guidelines for clinical practice. Methods: Using the National Health Insurance Research Database of Taiwan, COPD patients with or without bronchiectasis from 2000 to 2009 were enrolled as the BCO and COPD alone cohorts, respectively. Patients followed for <28 days, diagnosed with COPD who were not prescribed with COPD medications, and those diagnosed with bronchiectasis who did not receive a chest X-ray or computed tomography were excluded. The primary endpoints were acute exacerbations and mortality. Results: There were 831 patients in the BCO cohort and 3321 patients in the COPD alone cohort, covering 3763.08 and 17,348.95 person-years, respectively, from 2000 to 2011. The BCO cohort had higher risk for exacerbations (adjusted hazard ratio (HR) 2.26, 95% confidence interval (CI) 1.94–2.63) and mortality (HR 1.46, 95% CI 1.24–1.73) than the COPD alone cohort. In the patients overall, the use of statins, macrolides, and mucolytic agents was associated with significantly lower risks of acute exacerbations (statins, HR 0.37, 95% CI 0.29–0.46; macrolides, HR 0.65, 95% CI 0.45–0.93; mucolytic agents, HR 0.68, 95% CI 0.59–0.78). Statins were associated with a significantly lower risk of mortality (HR 0.32, 95% CI 0.25–0.41). In the BCO group, statins and mucolytic agents use was associated with significantly lower risks of acute exacerbations (statins, HR 0.44, 95% CI 0.29–0.65; mucolytic agents, HR 0.58, 95% CI 0.45–0.75). Conclusion: Statins and mucolytic agents use may lower risk of acute exacerbation in patients with BCO. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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11 pages, 1410 KiB  
Article
Fatigue is Highly Prevalent in Patients with Asthma and Contributes to the Burden of Disease
by Maarten Van Herck, Martijn A. Spruit, Chris Burtin, Remco Djamin, Jeanine Antons, Yvonne M. J. Goërtz, Zjala Ebadi, Daisy J. A. Janssen, Jan H. Vercoulen, Jeannette B. Peters, Melissa S. Y. Thong, Jacqueline Otker, Arnold Coors, Mirjam A. G. Sprangers, Jean W. M. Muris, Emiel F. M. Wouters and Alex J. Van ’t Hul
J. Clin. Med. 2018, 7(12), 471; https://doi.org/10.3390/jcm7120471 - 23 Nov 2018
Cited by 35 | Viewed by 6134
Abstract
The 2018 update of the Global Strategy for Asthma Management and Prevention does not mention fatigue-related symptoms. Nevertheless, patients with asthma frequently report tiredness, lack of energy, and daytime sleepiness. Quantitative research regarding the prevalence of fatigue in asthmatic patients is lacking. This [...] Read more.
The 2018 update of the Global Strategy for Asthma Management and Prevention does not mention fatigue-related symptoms. Nevertheless, patients with asthma frequently report tiredness, lack of energy, and daytime sleepiness. Quantitative research regarding the prevalence of fatigue in asthmatic patients is lacking. This retrospective cross-sectional study of outpatients with asthma upon referral to a chest physician assessed fatigue (Checklist Individual Strength-Fatigue (CIS-Fatigue)), lung function (spirometry), asthma control (Asthma Control Questionnaire (ACQ)), dyspnea (Medical Research Council (MRC) scale), exercise capacity (six-minute walk test (6MWT)), and asthma-related Quality-of-Life (QoL), Asthma Quality of Life Questionnaire (AQLQ) during a comprehensive health-status assessment. In total, 733 asthmatic patients were eligible and analyzed (47.4 ± 16.3 years, 41.1% male). Severe fatigue (CIS-Fatigue ≥ 36 points) was detected in 62.6% of patients. Fatigue was not related to airflow limitation (FEV1, ρ = −0.083); was related moderately to ACQ (ρ = 0.455), AQLQ (ρ = −0.554), and MRC (ρ = 0.435; all p-values < 0.001); and was related weakly to 6MWT (ρ = −0.243, p < 0.001). In stepwise multiple regression analysis, 28.9% of variance in fatigue was explained by ACQ (21.0%), MRC (6.5%), and age (1.4%). As for AQLQ, 42.2% of variance was explained by fatigue (29.8%), MRC (8.6%), exacerbation rate (2.6%), and age (1.2%). Severe fatigue is highly prevalent in asthmatic patients; it is an important determinant of disease-specific QoL and a crucial yet ignored patient-related outcome in patients with asthma. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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18 pages, 3238 KiB  
Article
Effects of Macrolide Treatment during the Hospitalization of Children with Childhood Wheezing Disease: A Systematic Review and Meta-Analysis
by Chien-Yu Lin, Tzu-Lin Yeh, Shu-Jung Liu, Hsin-Hui Lin, Yu-Jyun Cheng, Hua-His Hung, Mu-Chieh Tsai, Jui-Ming Liu and Wei-Te Lei
J. Clin. Med. 2018, 7(11), 432; https://doi.org/10.3390/jcm7110432 - 09 Nov 2018
Cited by 5 | Viewed by 4153
Abstract
Children are susceptible to a variety of respiratory infections. Wheezing is a common sign presented by children with respiratory infections. Asthma, bronchiolitis, and bronchitis are common causes of childhood wheezing disease (CWD) and are regarded as overlapping disease spectra. Macrolides are common antimicrobial [...] Read more.
Children are susceptible to a variety of respiratory infections. Wheezing is a common sign presented by children with respiratory infections. Asthma, bronchiolitis, and bronchitis are common causes of childhood wheezing disease (CWD) and are regarded as overlapping disease spectra. Macrolides are common antimicrobial agents with anti-inflammatory effects. We conducted a comprehensive literature search and a systematic review of studies that investigated the influences of macrolide treatment on CWD. The primary outcomes were the impact of macrolides on hospitalization courses of patients with CWD. Data pertaining to the study population, macrolide treatment, hospital courses, and recurrences were analyzed. Twenty-three studies with a combined study population of 2210 patients were included in the systematic review. Any kind of benefit from macrolide treatment was observed in approximately two-thirds of the studies (15/23). Eight studies were included in the meta-analysis to investigate the influence of macrolides on the length of stay (LOS), duration of oxygen demand (DOD), symptoms and signs of respiratory distress, and re-admission rates. Although the benefits of macrolide treatment were reported in several of the studies, no significant differences in LOS, DOD, symptoms and signs of respiratory distress, or re-admission rates were observed in patients undergoing macrolide treatment. In conclusion, any kind of benefit of macrolide treatment was observed in approximately two-thirds of the studies; however, no obvious benefits of macrolide treatment were observed in the hospitalization courses of children with CWD. The routine use of macrolides to improve the hospitalization course of children with CWD is not suggested. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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22 pages, 4459 KiB  
Article
The Anti-Inflammatory Effects of Fermented Herbal Roots of Asparagus cochinchinensis in an Ovalbumin-Induced Asthma Model
by Jun Young Choi, Ji Eun Kim, Jin Ju Park, Mi Rim Lee, Bo Ram Song, Ji Won Park, Mi Ju Kang, Hee Seob Lee, Hong Joo Son, Jin Tae Hong and Dae Youn Hwang
J. Clin. Med. 2018, 7(10), 377; https://doi.org/10.3390/jcm7100377 - 22 Oct 2018
Cited by 15 | Viewed by 4194
Abstract
Introduction: Roots of Asparagus cochinchinensis, which have pharmacologically active ingredients, have received great attention because they show good therapeutic effects for various inflammatory diseases without specific toxicity. This study investigated the anti-asthmatic effects of a butanol extract of Asparagus cochinchinensis roots that [...] Read more.
Introduction: Roots of Asparagus cochinchinensis, which have pharmacologically active ingredients, have received great attention because they show good therapeutic effects for various inflammatory diseases without specific toxicity. This study investigated the anti-asthmatic effects of a butanol extract of Asparagus cochinchinensis roots that had been fermented with Weissella cibaria (BAW) and its possible underlying cholinergic regulation. Methods: Alterations of the anti-asthmatic markers and the molecular response factors were measured in an ovalbumin (OVA)-induced asthma model after treatment with BAW. Results: Treatment with BAW decreased the intracellular reactive oxygen species (ROS) production in lipopolysaccharides (LPS) activated RAW264.7 cells. The results of the animal experiments revealed lower infiltration of inflammatory cells and bronchial thickness, and a significant reduction in the number of macrophages and eosinophils, concentration of OVA-specific IgE, and expression of Th2 cytokines in the OVA + BAW treated group. In addition, a significant recovery of goblet cell hyperplasia, MMP-9 expression, and the VEGF signaling pathway was observed upon airway remodeling in the OVA + BAW treated group. Furthermore, these responses of BAW were linked to recovery of acetylcholine esterase (AChE) activity and muscarinic acetylcholine receptor (mAChR) M3 downstream signaling pathway in epithelial cells, smooth muscle cells, and afferent sensory nerves of OVA + BAW-treated mice. Conclusion: Overall, these findings are the first to provide evidence that the therapeutic effects of BAW can prevent airway inflammation and remodeling through the recovery of cholinergic regulation in structural cells and inflammatory cells of the chronic asthma model. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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13 pages, 8303 KiB  
Article
Translational Medicine in Pulmonary-Renal Crosstalk: Therapeutic Targeting of p-Cresyl Sulfate Triggered Nonspecific ROS and Chemoattractants in Dyspneic Patients with Uremic Lung Injury
by Jia-Feng Chang, Shih-Shin Liang, Pounraj Thanasekaran, Hsueh-Wei Chang, Li-Li Wen, Chung-Hua Chen, Jian-Chiun Liou, Jih-Chen Yeh, Shih-Hao Liu, Huei-Min Dai and Wei-Ning Lin
J. Clin. Med. 2018, 7(9), 266; https://doi.org/10.3390/jcm7090266 - 09 Sep 2018
Cited by 22 | Viewed by 5640
Abstract
Molecular mechanisms and pathological features of p-Cresyl sulfate (PCS)-induced uremic lung injury (ULI) in chronic kidney disease (CKD) remain unclear. We analyzed pleural effusions (PE) from CKD and non-CKD patients for uremic toxins, reactive oxygen species (ROS), and chemotactic cytokines. Correlations between PE [...] Read more.
Molecular mechanisms and pathological features of p-Cresyl sulfate (PCS)-induced uremic lung injury (ULI) in chronic kidney disease (CKD) remain unclear. We analyzed pleural effusions (PE) from CKD and non-CKD patients for uremic toxins, reactive oxygen species (ROS), and chemotactic cytokines. Correlations between PE biomarkers and serum creatinine were also studied. Cell viability and inflammatory signaling pathways were investigated in PCS-treated human alveolar cell model. To mimic human diseases, CKD-ULI mouse model was developed with quantitative comparison of immunostaining and morphometric approach. PE from CKD patients enhance expressions of uremic toxins, hydroxyl radicals, and IL-5/IL-6/IL-8/IL-10/IL-13/ENA-78/GRO α/MDC/thrombopoietin/VEGF. PE concentrations of ENA-78/VEGF/IL-8/MDC/PCS/indoxyl sulphate correlate with serum creatinine concentrations. In vitro, PCS promotes alveolar cell death, cPLA2/COX-2/aquaporin-4 expression, and NADPH oxidase/mitochondria activation-related ROS. Intracellular ROS is abrogated by non-specific ROS scavenger N-acetyl cysteine (NAC), inhibitors of NADPH oxidase and mitochondria-targeted superoxide scavenger. However, only NAC protects against PCS-induced cell death. In vivo, expressions of cPLA2/COX2/8-OHdG, resident alveolar macrophages, recruited leukocytes, alveolar space, interstitial edema and capillary leakage increase in lung tissues of CKD-ULI mice, and NAC pretreatment ameliorates alveolar–capillary injury. PCS causes alveolar–capillary injury through triggering intracellular ROS, downstream prostaglandin pathways, cell death, and activating leukocytes to release multiplex chemoattractants and extracellular ROS. Thus PCS and nonspecific ROS serve as potential therapeutic targets. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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12 pages, 987 KiB  
Article
Metformin Decreases Risk of Tuberculosis Infection in Type 2 Diabetes Patients
by Chin-Hsiao Tseng
J. Clin. Med. 2018, 7(9), 264; https://doi.org/10.3390/jcm7090264 - 09 Sep 2018
Cited by 49 | Viewed by 5099
Abstract
Background: Metformin may show an antibiotic effect, but whether its use can reduce the risk of tuberculosis infection has rarely been investigated in population-based studies. Methods: This is a retrospective cohort analysis of the Taiwan’s National Health Insurance database. New-onset type 2 diabetes [...] Read more.
Background: Metformin may show an antibiotic effect, but whether its use can reduce the risk of tuberculosis infection has rarely been investigated in population-based studies. Methods: This is a retrospective cohort analysis of the Taiwan’s National Health Insurance database. New-onset type 2 diabetes patients, 148,468 ever users and 15,799 never users of metformin, identified during 1999–2005 were followed up until 31 December 2011 for the incidence of tuberculosis infection. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results: A total of 360 never users and 1976 ever users developed a tuberculosis infection with respective incidence of 510.91 and 282.94 per 100,000 person–years. The overall hazard ratio of presenting a tuberculosis infection among metformin ever users in respect to never users was 0.552 (95% confidence interval: 0.493–0.617). The hazard ratios for the first (<27.10 months), second (27.10–58.27 months), and third (>58.27 months) tertile of cumulative duration of metformin therapy were 1.116 (0.989–1.261), 0.543 (0.478–0.618), and 0.200 (0.171–0.233), respectively; and were 1.037 (0.918–1.173), 0.533 (0.469–0.606), and 0.249 (0.215–0.288), respectively, for the first (<817,000 mg), second (817,000–2,047,180 mg), and third (>2,047,180 mg) tertile of cumulative doses of metformin. The findings were consistent when analyses were restricted to pulmonary tuberculosis. Additionally, regular users of metformin tended to have greater benefit than irregular users. Conclusions: Metformin use is associated with a reduced risk of tuberculosis infection in a dose–response pattern in type 2 diabetes patients. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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Review

Jump to: Editorial, Research

14 pages, 826 KiB  
Review
Cardiovascular Comorbidities in Chronic Obstructive Pulmonary Disease (COPD)—Current Considerations for Clinical Practice
by Frederik Trinkmann, Joachim Saur, Martin Borggrefe and Ibrahim Akin
J. Clin. Med. 2019, 8(1), 69; https://doi.org/10.3390/jcm8010069 - 10 Jan 2019
Cited by 36 | Viewed by 11522
Abstract
In patients with chronic obstructive pulmonary disease (COPD), cardiovascular comorbidities are highly prevalent and associated with considerable morbidity and mortality. This coincidence is increasingly seen in context of a “cardiopulmonary continuum” rather than being simply attributed to shared risk factors such as cigarette [...] Read more.
In patients with chronic obstructive pulmonary disease (COPD), cardiovascular comorbidities are highly prevalent and associated with considerable morbidity and mortality. This coincidence is increasingly seen in context of a “cardiopulmonary continuum” rather than being simply attributed to shared risk factors such as cigarette smoking. Overlapping symptoms such as dyspnea or chest pain lead to a worse prognosis due to missed concomitant diagnoses. Moreover, medication is often withheld as a result of unfounded concerns about side effects. Despite the frequent coincidence, current guidelines are still mostly restricted to the management of the individual disease. Future diagnostic and therapeutic strategies should therefore be guided by an integrative perspective as well as a refined phenotyping of disease entities. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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27 pages, 1721 KiB  
Review
Interstitial Lung Disease and Pulmonary Fibrosis: A Practical Approach for General Medicine Physicians with Focus on the Medical History
by Or Kalchiem-Dekel, Jeffrey R. Galvin, Allen P. Burke, Sergei P. Atamas and Nevins W. Todd
J. Clin. Med. 2018, 7(12), 476; https://doi.org/10.3390/jcm7120476 - 24 Nov 2018
Cited by 53 | Viewed by 23561
Abstract
Interstitial lung disease (ILD) and pulmonary fibrosis comprise a wide array of inflammatory and fibrotic lung diseases which are often confusing to general medicine and pulmonary physicians alike. In addition to the myriad of clinical and radiologic nomenclature used in ILD, histopathologic descriptors [...] Read more.
Interstitial lung disease (ILD) and pulmonary fibrosis comprise a wide array of inflammatory and fibrotic lung diseases which are often confusing to general medicine and pulmonary physicians alike. In addition to the myriad of clinical and radiologic nomenclature used in ILD, histopathologic descriptors may be particularly confusing, and are often extrapolated to radiologic imaging patterns which may further add to the confusion. We propose that rather than focusing on precise histologic findings, focus should be on identifying an accurate etiology of ILD through a comprehensive and detailed medical history. Histopathologic patterns from lung biopsy should not be dismissed, but are often nonspecific, and overall treatment strategy and prognosis are likely to be determined more by the specific etiology of ILD rather than any particular histologic pattern. In this review, we outline a practical approach to common ILDs, highlight important aspects in obtaining an exposure history, clarify terminology and nomenclature, and discuss six common subgroups of ILD likely to be encountered by general medicine physicians in the inpatient or outpatient setting: Smoking-related, hypersensitivity pneumonitis, connective tissue disease-related, occupation-related, medication-induced, and idiopathic pulmonary fibrosis. Accurate diagnosis of these forms of ILD does require supplementing the medical history with results of the physical examination, autoimmune serologic testing, and chest radiographic imaging, but the importance of a comprehensive environmental, avocational, occupational, and medication-use history cannot be overstated and is likely the single most important factor responsible for achieving the best possible outcomes for patients. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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30 pages, 948 KiB  
Review
Drug-Induced Interstitial Lung Disease: A Systematic Review
by Sarah Skeoch, Nicholas Weatherley, Andrew J. Swift, Alexander Oldroyd, Christopher Johns, Conal Hayton, Alessandro Giollo, James M. Wild, John C. Waterton, Maya Buch, Kim Linton, Ian N. Bruce, Colm Leonard, Stephen Bianchi and Nazia Chaudhuri
J. Clin. Med. 2018, 7(10), 356; https://doi.org/10.3390/jcm7100356 - 15 Oct 2018
Cited by 211 | Viewed by 24727
Abstract
Background: Drug-induced interstitial lung disease (DIILD) occurs as a result of numerous agents, but the risk often only becomes apparent after the marketing authorisation of such agents. Methods: In this PRISMA-compliant systematic review, we aimed to evaluate and synthesise the current literature on [...] Read more.
Background: Drug-induced interstitial lung disease (DIILD) occurs as a result of numerous agents, but the risk often only becomes apparent after the marketing authorisation of such agents. Methods: In this PRISMA-compliant systematic review, we aimed to evaluate and synthesise the current literature on DIILD. Results: Following a quality assessment, 156 full-text papers describing more than 6000 DIILD cases were included in the review. However, the majority of the papers were of low or very low quality in relation to the review question (78%). Thus, it was not possible to perform a meta-analysis, and descriptive review was undertaken instead. DIILD incidence rates varied between 4.1 and 12.4 cases/million/year. DIILD accounted for 3–5% of prevalent ILD cases. Cancer drugs, followed by rheumatology drugs, amiodarone and antibiotics, were the most common causes of DIILD. The radiopathological phenotype of DIILD varied between and within agents, and no typical radiological pattern specific to DIILD was identified. Mortality rates of over 50% were reported in some studies. Severity at presentation was the most reliable predictor of mortality. Glucocorticoids (GCs) were commonly used to treat DIILD, but no prospective studies examined their effect on outcome. Conclusions: Overall high-quality evidence in DIILD is lacking, and the current review will inform larger prospective studies to investigate the diagnosis and management of DIILD. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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21 pages, 1658 KiB  
Review
Clinical Application of Mesenchymal Stem Cell-Derived Extracellular Vesicle-Based Therapeutics for Inflammatory Lung Diseases
by Yu Fujita, Tsukasa Kadota, Jun Araya, Takahiro Ochiya and Kazuyoshi Kuwano
J. Clin. Med. 2018, 7(10), 355; https://doi.org/10.3390/jcm7100355 - 14 Oct 2018
Cited by 124 | Viewed by 8047
Abstract
It is currently thought that extracellular vesicles (EVs), such as exosomes and microvesicles, play an important autocrine/paracrine role in intercellular communication. EVs package proteins, mRNA and microRNA (miRNA), which have the ability to transfer biological information to recipient cells in the lungs. Depending [...] Read more.
It is currently thought that extracellular vesicles (EVs), such as exosomes and microvesicles, play an important autocrine/paracrine role in intercellular communication. EVs package proteins, mRNA and microRNA (miRNA), which have the ability to transfer biological information to recipient cells in the lungs. Depending on their origin, EVs fulfil different functions. EVs derived from mesenchymal stem cells (MSCs) have been found to promote therapeutic activities that are comparable to MSCs themselves. Recent animal model-based studies suggest that MSC-derived EVs have significant potential as a novel alternative to whole-cell therapies. Compared to their parent cells, EVs may have a superior safety profile and can be stored without losing function. It has been observed that MSC-derived EVs suppress pro-inflammatory processes and reduce oxidative stress, pulmonary fibrosis and remodeling in a variety of in vivo inflammatory lung disease models by transferring their components. However, there remain significant challenges to translate this therapy to the clinic. From this view point, we will summarize recent studies on EVs produced by MSCs in preclinical experimental models of inflammatory lung diseases. We will also discuss the most relevant issues in bringing MSC-derived EV-based therapeutics to the clinic for the treatment of inflammatory lung diseases. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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20 pages, 1087 KiB  
Review
Proteases and Their Inhibitors in Chronic Obstructive Pulmonary Disease
by Tapan Dey, Jatin Kalita, Sinéad Weldon and Clifford C. Taggart
J. Clin. Med. 2018, 7(9), 244; https://doi.org/10.3390/jcm7090244 - 28 Aug 2018
Cited by 36 | Viewed by 7250
Abstract
In the context of respiratory disease, chronic obstructive pulmonary disease (COPD) is the leading cause of mortality worldwide. Despite much development in the area of drug development, currently there are no effective medicines available for the treatment of this disease. An imbalance in [...] Read more.
In the context of respiratory disease, chronic obstructive pulmonary disease (COPD) is the leading cause of mortality worldwide. Despite much development in the area of drug development, currently there are no effective medicines available for the treatment of this disease. An imbalance in the protease: Antiprotease ratio in the COPD lung remains an important aspect of COPD pathophysiology and several studies have shown the efficacy of antiprotease therapy in both in vitro and in vivo COPD models. However more in-depth studies will be required to validate the efficacy of lead drug molecules targeting these proteases. This review discusses the current status of protease-directed drugs used for treating COPD and explores the future prospects of utilizing the potential of antiprotease-based therapeutics as a treatment for this disease. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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21 pages, 1093 KiB  
Review
Idiopathic Pulmonary Fibrosis (IPF): An Overview
by Shaney L. Barratt, Andrew Creamer, Conal Hayton and Nazia Chaudhuri
J. Clin. Med. 2018, 7(8), 201; https://doi.org/10.3390/jcm7080201 - 06 Aug 2018
Cited by 203 | Viewed by 22327
Abstract
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterised by chronic, progressive scarring of the lungs and the pathological hallmark of usual interstitial pneumonia. Current paradigms suggest alveolar epithelial cell damage is a key initiating factor. Globally, incidence of the disease is [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterised by chronic, progressive scarring of the lungs and the pathological hallmark of usual interstitial pneumonia. Current paradigms suggest alveolar epithelial cell damage is a key initiating factor. Globally, incidence of the disease is rising, with associated high morbidity, mortality, and economic healthcare burden. Diagnosis relies on a multidisciplinary team approach with exclusion of other causes of interstitial lung disease. Over recent years, two novel antifibrotic therapies, pirfenidone and nintedanib, have been developed, providing treatment options for many patients with IPF, with several other agents in early clinical trials. Current efforts are directed at identifying key biomarkers that may direct more customized patient-centred healthcare to improve outcomes for these patients in the future. Full article
(This article belongs to the Special Issue Lung Disease on COPD, Asthma, Bronchiectasis, Lung Cancer Screening, IPF)
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