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Wang C, Liu Z, Ren X, Li Y, Sun L. Screening of cytokines-cytokine receptor-associated genes in childhood asthma based on bioinformatics. Integr Biol (Camb) 2025; 17:zyaf002. [PMID: 40036607 DOI: 10.1093/intbio/zyaf002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 11/20/2024] [Accepted: 01/23/2025] [Indexed: 03/06/2025]
Abstract
PURPOSE To develop efficient diagnostic and treatment approaches, gaining an in-depth knowledge of the molecular mechanisms and potential targets causing childhood asthma is of utmost significance. METHODS Childhood asthma datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between asthmatic child and healthy people were screened by the Limma package. DEGs were subjected to further analyses utilizing GO, KEGG and GSEA analysis. The hub genes associated with childhood asthma were discovered by PPI analysis. The drugs target hub genes were accessed from the DrugBank database. Autodock vina was used to explore the binding ability of targeted drugs to hub genes. RESULTS Total 80 DEGs were selected from GSE152004 and GSE65204 datasets. The cytokine-cytokine receptor interaction was the key pathway identified by functional enrichment analysis of shared DEGs. A total of 4 hub genes (CCL26, CXCR6, IL18RAP and CCL20) were identified by the constructed PPI network, among which CXCR6, IL18RAP and CCL20 were significantly decreased in childhood asthma datasets. Whereas, the CCL26 was significantly increased in childhood asthma datasets. Additionally, the extra dataset GSE19187 and GSE240567 were employed for validation. Ultimately, drugs (Cimetidine, Cefaclor and Propofol) that target hub genes have favorable combination ability. CONCLUSIONS We have determined that CCL26, CXCR6, IL18RAP and CCL20 might have crucial involvement in the advancement of childhood asthma, thus having the potential to be targeted therapeutically in order to enhance treatment choices for childhood asthma. Statement of Integration, Innovation and Insight: The cytokine-cytokine receptor interaction is a key pathway in the occurrence of childhood asthma. The hub genes (CCL26, CXCR6, IL18RAP and CCL20) affect the development of childhood asthma. The drugs (Cimetidine, Cefaclor and Propofol) that target hub genes have favorable combination ability.
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Affiliation(s)
- Caiwen Wang
- Changchun University of Chinese Medicine, No. 1035, Boshuo Road, Jingyue High tech Industrial Development District, Changchun City Jilin Province 130117, China
| | - Zhimei Liu
- Children's Diagnosis and Treatment Center, The Affiliated Hospital to Changchun University of Chinese Medicine, No. 185, Shenzhen Street, Erdao District, Changchun City Jilin Province 130000, China
| | - Xiaoting Ren
- Children's Diagnosis and Treatment Center, The Affiliated Hospital to Changchun University of Chinese Medicine, No. 185, Shenzhen Street, Erdao District, Changchun City Jilin Province 130000, China
| | - Yiquan Li
- Changchun University of Chinese Medicine, No. 1035, Boshuo Road, Jingyue High tech Industrial Development District, Changchun City Jilin Province 130117, China
| | - Liping Sun
- Changchun University of Chinese Medicine, No. 1035, Boshuo Road, Jingyue High tech Industrial Development District, Changchun City Jilin Province 130117, China
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Abstract
Gastroesophageal reflux (GER) is a normal physiologic process. It is important to distinguish GER from GER disease (GERD) since GER does not require treatment. Although a diagnosis of GERD can largely be based on history and physical alone, endoscopy and pH impedance studies can help make the diagnosis when there in atypical presentation. In children and adolescents, lifestyle changes and acid suppression are first-line treatments for GERD. In infants, acid suppression is not effective, but a trial of hydrolyzed formula can be considered, as milk protein sensitivity can be difficult to differentiate from GER symptoms.
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Affiliation(s)
- Hayat Mousa
- University of California, San Diego, 3020 Children’s Way, MOB 211, MC
5030, San Diego, CA 92123,
| | - Maheen Hassan
- University of California, San Diego, 3020 Children’s Way, MOB 211,
MC 5030, San Diego, CA 92123,
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Turner AM, Tamasi L, Schleich F, Hoxha M, Horvath I, Louis R, Barnes N. Clinically relevant subgroups in COPD and asthma. Eur Respir Rev 2016; 24:283-98. [PMID: 26028640 DOI: 10.1183/16000617.00009014] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
As knowledge of airways disease has grown, it has become apparent that neither chronic obstructive pulmonary disease (COPD) nor asthma is a simple, easily defined disease. In the past, treatment options for both diseases were limited; thus, there was less need to define subgroups. As treatment options have grown, so has our need to predict who will respond to new drugs. To date, identifying subgroups has been largely reported by detailed clinical characterisation or differences in pathobiology. These subgroups are commonly called "phenotypes"; however, the problem of defining what constitutes a phenotype, whether this should include comorbid diseases and how to handle changes over time has led to the term being used loosely. In this review, we describe subgroups of COPD and asthma patients whose clinical characteristics we believe have therapeutic or major prognostic implications specific to the lung, and whether these subgroups are constant over time. Finally, we will discuss whether the subgroups we describe are common to both asthma and COPD, and give some examples of how treatment might be tailored in patients where the subgroup is clear, but the label of asthma or COPD is not.
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Affiliation(s)
- Alice M Turner
- Clinical and Experimental Medicine, University of Birmingham, Queen Elizabeth Hospital Birmingham, Birmingham, UK Dept of Respiratory Medicine, Birmingham Heartlands Hospital, Birmingham, UK
| | - Lilla Tamasi
- Dept of Pulmonology, Semmelweis University, Budapest, Hungary
| | | | - Mehmet Hoxha
- Service of Allergology and Clinical Immunology, UHC "Mother Teresa", Tirana, Albania
| | - Ildiko Horvath
- Dept of Pulmonology, Semmelweis University, Budapest, Hungary
| | - Renaud Louis
- Respiratory Medicine, CHU Sart-Tilman B35, Liege, Belgium
| | - Neil Barnes
- GlaxoSmithKline, Stockley Park West, Uxbridge, UK
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Guimarães EV, Guerra PV, Penna FJ. Management of gastroesophageal reflux disease and erosive esophagitis in pediatric patients: focus on delayed-release esomeprazole. Ther Clin Risk Manag 2010; 6:531-7. [PMID: 21063463 PMCID: PMC2963162 DOI: 10.2147/tcrm.s14425] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVE To review the literature on the treatment of gastroesophageal reflux disease (GERD) with emphasis on proton pump inhibitors (PPIs), particularly on delayed-release esomeprazole, and to identify properties and adverse effects of PPIs observed in the treatment of GERD in children and adolescents. SOURCES Electronic search of PubMed/Medline and Cochrane Collaboration databases, and of abstracts on DDW, NASPGHAN, and ESPGHAN. We focused on controlled and randomized studies published since 2000 and identified reviews that presented a consensual position, and directives published within the last 10 years. MAIN RESULTS PPIs are considered better antisecretory agents than H(2)-receptor antagonists. Although all PPIs are similar, they are not identical in their pharmacologic properties. For example, the acid-suppressive effect of esomeprazole, the S-isomer of omeprazole, persists for more than 16 hours after administration of the morning dose. Therefore, it can control acidity after night meals better than a single dose of omeprazole. Moreover, the onset of the suppressive effect of esomeprazole is faster. It achieves acid inhibition faster than other PPIs. CONCLUSION Currently, the mainstream treatment for GERD in children is a PPI. Although PPIs are safe drugs, effective in healing erosive esophagitis, and in relieving symptoms, studies with esomeprazole have shown that this drug has as powerful an ability to inhibit acid secretion as omeprazole. It also seems that some pharmacologic properties of esomeprazole are actually better for the treatment of GERD.
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Affiliation(s)
- Elizabet V Guimarães
- Department of Pediatrics, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr 2009; 49:498-547. [PMID: 19745761 DOI: 10.1097/mpg.0b013e3181b7f563] [Citation(s) in RCA: 495] [Impact Index Per Article: 30.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To develop a North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) international consensus on the diagnosis and management of gastroesophageal reflux and gastroesophageal reflux disease in the pediatric population. METHODS An international panel of 9 pediatric gastroenterologists and 2 epidemiologists were selected by both societies, which developed these guidelines based on the Delphi principle. Statements were based on systematic literature searches using the best-available evidence from PubMed, Cumulative Index to Nursing and Allied Health Literature, and bibliographies. The committee convened in face-to-face meetings 3 times. Consensus was achieved for all recommendations through nominal group technique, a structured, quantitative method. Articles were evaluated using the Oxford Centre for Evidence-based Medicine Levels of Evidence. Using the Oxford Grades of Recommendation, the quality of evidence of each of the recommendations made by the committee was determined and is summarized in appendices. RESULTS More than 600 articles were reviewed for this work. The document provides evidence-based guidelines for the diagnosis and management of gastroesophageal reflux and gastroesophageal reflux disease in the pediatric population. CONCLUSIONS This document is intended to be used in daily practice for the development of future clinical practice guidelines and as a basis for clinical trials.
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Sea J, Teichman JMH. Paediatric painful bladder syndrome/interstitial cystitis: diagnosis and treatment. Drugs 2009; 69:279-96. [PMID: 19275272 DOI: 10.2165/00003495-200969030-00004] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
To describe the pathophysiology, diagnosis and controversies surrounding the diagnosis and pharmacological treatments of painful bladder syndrome/interstitial cystitis (PBS/IC) in children, we reviewed adult and paediatric literature pertaining to PBS/IC. Paediatric PBS/IC presents similarly to adult PBS/IC. The diagnosis is made by exclusion. Paediatric PBS/IC patients complain most commonly of urinary frequency, and abdominal pain occurs in up to 88% of affected children. Enuresis may also be a presenting complaint. Urinalysis and urine cultures are unremarkable. Management of paediatric PBS/IC is similar to that of adult PBS/IC, and non-surgical management includes dietary, lifestyle and pharmacological therapy. Pharmacological options include pentosan polysulfate, amitriptyline, hydroxyzine, cimetidine or intravesical therapies (dimethyl sulfoxide or 'therapeutic solution').
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Affiliation(s)
- Jason Sea
- Division of Urology, Providence Healthcare and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada
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Bonatti H, Achem SR, Hinder RA. Impact of changing epidemiology of gastroesophageal reflux disease on its diagnosis and treatment. J Gastrointest Surg 2008; 12:373-81. [PMID: 17846850 DOI: 10.1007/s11605-007-0294-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Gastroesophageal reflux disease (GERD) has emerged as one of the most common diseases in modern civilization. This article reviews selected changes in epidemiology of GERD during the past decade and provides information on treatment options with a focus on the impact of GERD and potential role of laparoscopic antireflux surgery in patients with diabetes mellitus, obesity, liver cirrhosis, at the extremes of life age and in immunocompromised individuals such as liver and lung transplant recipients.
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Affiliation(s)
- Hugo Bonatti
- Department of Surgery, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA
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Abstract
PURPOSE OF REVIEW To summarize and contextualize current concepts in the incidence, diagnosis, management and long-term sequelae of extraesophageal reflux disease in children. RECENT FINDINGS Extraesophageal reflux disease is a different disease entity from gastroesophageal reflux disease. The two diseases have a common etiology, refluxate causing mucosal damage, but the extent and location of the damage varies considerably depending on the underlying mucosal characteristics. Extraesophageal reflux disease in children is characterized by a broad set of symptoms and signs that vary according to age at presentation and severity of disease. Serious long-term effects begin in childhood. The role of pepsin, bile acids, pancreatic enzymes, motility disorders, and food allergies have only recently been recognized. Newer diagnostic modalities include multichannel intraluminal pH/impedance, the 48 h Bravo implantable probe, and hypopharyngeal pH monitoring. While proton pump inhibitors provide superior acid suppression compared with histamine-2 blockers, variability in response and lack of efficacy for alkaline refluxate often require other therapeutic interventions. SUMMARY Pediatric extraesophageal reflux disease has variable presentation and a gold standard test is still lacking. Primary treatment includes lifestyle and feeding changes and medical therapy. Ongoing monitoring for recurrence and agreement as to duration of therapy present significant challenges not yet standardized amongst practitioners.
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Affiliation(s)
- Linda Brodsky
- State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York 14222, USA.
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Bonatti H, Ferguson D, Wykypiel H, Aranda-Michel J, Achem SR, Hinder RA, DeVault K. Review on extraesophageal reflux disease. Eur Surg 2006. [DOI: 10.1007/s10353-006-0262-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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&NA;. Treat gastro-oesophageal reflux disease aggressively in children with asthma. DRUGS & THERAPY PERSPECTIVES 2006. [DOI: 10.2165/00042310-200622040-00003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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Di Ciaula A, Portincasa P, Di Terlizzi L, Paternostro D, Palasciano G. Ultrasonographic study of postcibal gastro-esophageal reflux and gastric emptying in infants with recurrent respiratory disease. World J Gastroenterol 2005; 11:7296-7301. [PMID: 16437631 PMCID: PMC4725147 DOI: 10.3748/wjg.v11.i46.7296] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2005] [Revised: 05/13/2005] [Accepted: 05/18/2005] [Indexed: 02/06/2023] Open
Abstract
AIM To check the utility of postcibal ultrasonography for the evaluation of reflux in relation to gastric emptying in infants with recurrent respiratory symptoms and to link imaging with clinical data. METHODS Esophageal reflux (hyperechoic retrograde filling) and gastric emptying (antral areas) were quantified before and after ingestion of a standard formula in 35 untreated infants (13 with chronic cough, 22 with recurrent bronchitis) and in 31 controls. RESULTS The prevalence of abnormal (> or =8 episodes) postcibal refluxes was 74% in patients and 3% in controls. Number, duration of the longest episode and extent of refluxes were significantly higher in patients compared to controls. Number of refluxes was higher in patients with symptomatic refluxes than in those without. Infants with recurrent bronchitis had more refluxes than those with chronic cough and controls. Extent and timing of gastric emptying were similar in patients and controls. CONCLUSION Esophageal ultrasonography is a useful and physiological test in infants with recurrent respiratory diseases, which have a high prevalence of abnormal postcibal esophageal reflux and a gastric emptying similar to that of normal controls. Esophageal reflux is more severe in subjects with recurrent bronchitis than in those with chronic cough.
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Affiliation(s)
- Agostino Di Ciaula
- Division of Internal Medicine, P.O. Bisceglie, 70052 Bisceglie (BA), Italy.
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Abstract
Obesity is an important public health problem. An increasing body of data supports the hypothesis that obesity is a risk factor for asthma. These data include numerous large cross-sectional and prospective studies performed in adults, adolescents, and children throughout the world. With few exceptions, these studies indicate an increased relative risk of asthma in the obese and overweight and demonstrate that obesity antedates asthma. Obesity appears to be a particularly important issue for severe asthma. Studies showing improvements in asthma in subjects who lose weight, as well as studies showing that obese mice have innate airway hyperresponsiveness (AHR) as well as increased responses to certain asthma triggers also suggest a causal relationship between obesity and asthma. The mechanistic basis for this relationship has not been established. It may be that obesity and asthma share some common etiology, such as a common genetic predisposition, common effects of in utero conditions, or that obesity and asthma are both the result of some other predisposing factor such as physical activity or diet. However, there are also plausible biological mechanisms whereby obesity could be expected to either cause or worsen asthma. These include co-morbidities such as gastroesophageal reflux, complications from sleep-disordered breathing (SDB), breathing at low lung volume, chronic systemic inflammation, and endocrine factors, including adipokines and reproductive hormones. Understanding the mechanistic basis for the relationship between obesity and asthma may lead to new therapeutic strategies for treatment of this susceptible population.
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Affiliation(s)
- Stephanie A Shore
- Physiology Program, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
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