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| ===== Introduction ===== | ===== Introduction ===== | ||
| - | **What is CD** | + | **What is Crohn's Disease (CD)?** |
| Crohn disease is an idiopathic, chronic inflammatory process of the gastrointestinal (GI) tract which affects any parts of the tract ranging from the mouth to the anus. It is believed to be the result of an imbalance between pro-inflammatory and anti-inflammatory mediators. Some factors which encourages this imbalance are genetic susceptibility and environmental triggers. Hence, there is no real single factor that induces this intestinal inflammation. | Crohn disease is an idiopathic, chronic inflammatory process of the gastrointestinal (GI) tract which affects any parts of the tract ranging from the mouth to the anus. It is believed to be the result of an imbalance between pro-inflammatory and anti-inflammatory mediators. Some factors which encourages this imbalance are genetic susceptibility and environmental triggers. Hence, there is no real single factor that induces this intestinal inflammation. | ||
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| http://www.nhlbi.nih.gov/health/health-topics/topics/copd> | http://www.nhlbi.nih.gov/health/health-topics/topics/copd> | ||
| - | <box width classes round white centre|>{{:action_of_beta-agonists.png|}}</box| Figure 13: Mechanism of Action of Beta-Agonists> | + | <box width classes round white centre|>{{:12021.png|}}</box| Figure 1: Inflammation of the Gastrointestinal (GI) Tract> |
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| On a microscopic level, the initial lesion starts from an ulceration of the superficial mucosa. The inflammatory cells such as granulomas then invade the deep mucosal layers and start extending through all layers of the intestinal walls and into the regional lymph nodes. Although granuloma formation is the primary pathophysiologic factor of Crohn disease, its absence does not exclude the diagnosis. | On a microscopic level, the initial lesion starts from an ulceration of the superficial mucosa. The inflammatory cells such as granulomas then invade the deep mucosal layers and start extending through all layers of the intestinal walls and into the regional lymph nodes. Although granuloma formation is the primary pathophysiologic factor of Crohn disease, its absence does not exclude the diagnosis. | ||
| - | <box width classes round white centre|>{{:improvement_of_lung_capacity.png|}}</box| Figure 15: Improvement of lung capacity, within the first 12-24 hours, in individuals with severe COPD after the ingestion of both long-acting beta-agonist’s and anticholingeric medications. Modified from: Van Noord et al. (2005)> | + | <box width classes round white centre|>{{:12022.png|}}</box| Figure 2: Invasion of granulosa cells inducing inflammation in GI tract.> |
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| Measles virus infection can disrupt immune function, mainly in helper T-cell response. Many studies show the role measles virus plays in the aetiology of inflammatory bowel diseases, like Crohn’s disease. A technique called immunogold electron microscopy has confirmed the persistence of measles in Crohn’s disease affected bowel. There is a positive relationship between perinatal exposure to measles and the development of CD (Thompson., Pounder., Wakefield., & Montgomery, 1995). | Measles virus infection can disrupt immune function, mainly in helper T-cell response. Many studies show the role measles virus plays in the aetiology of inflammatory bowel diseases, like Crohn’s disease. A technique called immunogold electron microscopy has confirmed the persistence of measles in Crohn’s disease affected bowel. There is a positive relationship between perinatal exposure to measles and the development of CD (Thompson., Pounder., Wakefield., & Montgomery, 1995). | ||
| - | <box width classes round white centre|>{{:action_of_anti-cholinergics.png|}}</box| Figure 14: Action of Anti-Cholinergics> | + | <box width classes round white centre|>{{:12023.png|}}</box| Figure 3: Measles virus infection is linked to the development of Crohn’s disease.> |
| **Breastfeeding** | **Breastfeeding** | ||
| Measles virus infection can disrupt immune function, mainly in helper T-cell response. Many studies show the role measles virus plays in the aetiology of inflammatory bowel diseases, like Crohn’s disease. A technique called immunogold electron microscopy has confirmed the persistence of measles in Crohn’s disease affected bowel. There is a positive relationship between perinatal exposure to measles and the development of CD (Thompson., Pounder., Wakefield., & Montgomery, 1995). | Measles virus infection can disrupt immune function, mainly in helper T-cell response. Many studies show the role measles virus plays in the aetiology of inflammatory bowel diseases, like Crohn’s disease. A technique called immunogold electron microscopy has confirmed the persistence of measles in Crohn’s disease affected bowel. There is a positive relationship between perinatal exposure to measles and the development of CD (Thompson., Pounder., Wakefield., & Montgomery, 1995). | ||
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| - | <box width classes round white centre|>{{:summary_of_pathways_and_candidate_genes_involved_in_copd.png|}}</box| Figure 3: Summary of Pathways and Candidate Genes Involved in COPD. Retrieved from: | ||
| - | http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.629.4676&rep=rep1&type=pdf> | ||
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| - | <box width classes round white centre|>{{:inflammatory_mechanisms_in_copd._macnee_2006_.png|}}</box| Figure 4. Inflammatory mechanisms in COPD. Modified from: MacNee (2006)> | ||
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| - | <box width classes round white centre|>{{:a._normal_small_airway_b._abnormal_small_airway_exhibiting_airway_remodeling_in_copd._berge_et_al._2011_.png|}}</box| Figure 5: A. Normal Small Airway, B. Abnormal Small Airway Exhibiting Airway Remodeling in COPD. Modified from: Berge et al. (2011)> | ||
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| - | ===== Medications ===== | + | ===== Medications- Prednisone ===== |
| **What is Prednisone?** | **What is Prednisone?** | ||
| Prednisone is a corticosteroid that acts as a glucocorticoid receptor agonist in order to treat inflammatory diseases, such as Crohn’s (Barnes, 1998). Inflammation of the digestive tract is a common symptom in Crohn’s disease patients due to the pathophysiology of this disease. In the past, corticosteroids like Prednisone have been used for their immunosuppressive and anti-inflammatory properties (Jobin & Sartor, 2000). They are able to decrease inflammation by inhibiting the actions of pro-inflammatory cytokines, thus decreasing recruitment of white blood cells, like monocytes and neutrophils, which cause inflammation (Auphan et al., 1995). Many studies have conclusively shown that pro-inflammatory cytokine, such as TNF- alpha and IFN-gamma, are responsible for the inflammation of the gastrointestinal tract that is present in Crohn’s disease patients (Wakefield et al., 1991). Typically, the anti-inflammatory response in the body is controlled by glucocorticoids. When their release is normally stimulated in the body, they will bind to intracellular, cytoplasmic glucocorticoid receptors (Farell & Kelleher, 2003). These receptors will dimerize upon binding and immediately be transported to the nucleus where the regulate the transcription of target genes through block transcription of the promote NF-kappa-B. As mentioned earlier, NF-kappa-B is a potent transcription factors that, when activated, will lead the production of pro-inflammatory cytokines like TNF-alpha (Beato, Herrlich & Schutz, 1995). Research into other inflammatory disorders, such as asthma and irritable bowel syndrome, have proven that these diseases are caused by glucocorticoid resistance, which leads to an un-regulated inflammatory response, caused by increased cytokines which increase recruitment of white blood cells (Barnes, 1998). Since inflammation is a primary part of the pathophysiology of Crohn’s disease, Prednisone can effectively manage these symptoms by binding to glucocorticoid receptors and promoting their activation. By doing do, Prednisone is able to inhibit inflammatory cytokine production and thus ultimately decrease white blood cell recruitment and inflammation (Barnes, 1998). | Prednisone is a corticosteroid that acts as a glucocorticoid receptor agonist in order to treat inflammatory diseases, such as Crohn’s (Barnes, 1998). Inflammation of the digestive tract is a common symptom in Crohn’s disease patients due to the pathophysiology of this disease. In the past, corticosteroids like Prednisone have been used for their immunosuppressive and anti-inflammatory properties (Jobin & Sartor, 2000). They are able to decrease inflammation by inhibiting the actions of pro-inflammatory cytokines, thus decreasing recruitment of white blood cells, like monocytes and neutrophils, which cause inflammation (Auphan et al., 1995). Many studies have conclusively shown that pro-inflammatory cytokine, such as TNF- alpha and IFN-gamma, are responsible for the inflammation of the gastrointestinal tract that is present in Crohn’s disease patients (Wakefield et al., 1991). Typically, the anti-inflammatory response in the body is controlled by glucocorticoids. When their release is normally stimulated in the body, they will bind to intracellular, cytoplasmic glucocorticoid receptors (Farell & Kelleher, 2003). These receptors will dimerize upon binding and immediately be transported to the nucleus where the regulate the transcription of target genes through block transcription of the promote NF-kappa-B. As mentioned earlier, NF-kappa-B is a potent transcription factors that, when activated, will lead the production of pro-inflammatory cytokines like TNF-alpha (Beato, Herrlich & Schutz, 1995). Research into other inflammatory disorders, such as asthma and irritable bowel syndrome, have proven that these diseases are caused by glucocorticoid resistance, which leads to an un-regulated inflammatory response, caused by increased cytokines which increase recruitment of white blood cells (Barnes, 1998). Since inflammation is a primary part of the pathophysiology of Crohn’s disease, Prednisone can effectively manage these symptoms by binding to glucocorticoid receptors and promoting their activation. By doing do, Prednisone is able to inhibit inflammatory cytokine production and thus ultimately decrease white blood cell recruitment and inflammation (Barnes, 1998). | ||
| - | <box width classes round white centre|>{{:nutrition.png|}}</box| Figure 7: Foods Full of Nutrition. Retrieved from: http://blog.copdstore.com/the-official-guide-to-copd-nutrition> | + | <box width classes round white centre|>{{:12024.png}}</box| Figure 4: The mechanism of action of prednisone. By blocking the promoter, NF-kappa-B, Prednisone is able to effectively prevent the transcription and production of pro-inflammatory genes while simultaneously promoting the transcription and production of anti-inflammatory genes.> |
| **Effectiveness** | **Effectiveness** | ||
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| - | <box width classes round white centre|>{{:pulmonary_rehabilitation_in_action.png|}}</box| Figure 8: Pulmonary Rehabilitation in Action. Retrieved from: http://drvijaynair.8m.com/ > | + | <box width classes round white centre|>{{:12025.png|}}</box| Figure 5: The reduction in LM ratios in Crohn’s disease patients, after treatment with Prednisone. This 50% of reduction is indicative of decreased intestinal permeability (Wild et al., 2003). > |
| - | <box width classes round white centre|>{{:pulmonary_rehabilitation_in_action.png|}}</box| Figure 8: Pulmonary Rehabilitation in Action. Retrieved from: http://drvijaynair.8m.com/ > | + | <box width classes round white centre|>{{:12026.png|}}</box| Figure 6: Pulmonary Rehabilitation in Action. Retrieved from: http://drvijaynair.8m.com/ > |
| **Side Effects** | **Side Effects** | ||
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| + | ===== Medications- Infliximab/ Remicade ===== | ||
| - | **What is Prednisone?** | + | **What is Prednisone/ Remicade?** |
| Kirman, Whelan, & Nielsen (2004) identify infliximab (trade name Remicade) is an IgG monoclonal antibody drug that targets TNF-alpha, a tumor necrosis factor. It is effective in ⅔ of Crohn’s Disease patients. The antibody is developed from mice and then replaced with human antibody domains (Kirman, Whelan, & Nielsen, 2004). Not only does infliximab treat Crohn’s Disease, but it also treats ulcerative colitis, psoriasis, psoriatic arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, plaque psoriasis (Janssen Biotech, 2016). Having an excess of TNF-alpha can cause the immune system to attack healthy cells in the GI tract leading to inflammation, and symptoms of Crohn’s Disease (Janssen Biotech, 2016). | Kirman, Whelan, & Nielsen (2004) identify infliximab (trade name Remicade) is an IgG monoclonal antibody drug that targets TNF-alpha, a tumor necrosis factor. It is effective in ⅔ of Crohn’s Disease patients. The antibody is developed from mice and then replaced with human antibody domains (Kirman, Whelan, & Nielsen, 2004). Not only does infliximab treat Crohn’s Disease, but it also treats ulcerative colitis, psoriasis, psoriatic arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, plaque psoriasis (Janssen Biotech, 2016). Having an excess of TNF-alpha can cause the immune system to attack healthy cells in the GI tract leading to inflammation, and symptoms of Crohn’s Disease (Janssen Biotech, 2016). | ||
| - | <box width classes round white centre|>{{:spirometry_traces_representing_healthy_patients_and_copd_patients.png|}}</box| Figure 6: Spirometry Traces Representing Healthy Patients and COPD Patients. Retrieved from: http://www.thinkcopdifferently.com/en/About-COPD/Diagnosing-COPD/Spirometric-assessment> | + | <box width classes round white centre|>{{:12027.png|}}</box| Figure 7: Infliximab. Modified from: http://www.peterbullartstudio.co.uk/webcontent/wp-content/gallery/technical/technical30.jpg> |
| ** Mechanism of Action ** | ** Mechanism of Action ** | ||
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| Infliximab binds to TNF-alpha expressing cells, as seen in Figure 8 (replace with real figure name), and precents TNF-alpha from binding to its receptor. The results of this drug are apoptosis of T-lymphocytes and monocytes, and down regulation of other inflammatory cytokines such as Th1 (Kirman, Whelan, & Nielsen, 2004). Apoptosis of monocytes is initiated by the CD95/CD95L signaling pathway and mitochondrial release of cytochrome C (Lügering et al., 2001). Cytochrome C release triggers the transcriptional activation of Bax and Bak, pro apoptotic regulators (Van Deventer, 2001). | Infliximab binds to TNF-alpha expressing cells, as seen in Figure 8 (replace with real figure name), and precents TNF-alpha from binding to its receptor. The results of this drug are apoptosis of T-lymphocytes and monocytes, and down regulation of other inflammatory cytokines such as Th1 (Kirman, Whelan, & Nielsen, 2004). Apoptosis of monocytes is initiated by the CD95/CD95L signaling pathway and mitochondrial release of cytochrome C (Lügering et al., 2001). Cytochrome C release triggers the transcriptional activation of Bax and Bak, pro apoptotic regulators (Van Deventer, 2001). | ||
| - | <box width classes round white centre|>{{:spirometry_traces_representing_healthy_patients_and_copd_patients.png|}}</box| Figure 6: Spirometry Traces Representing Healthy Patients and COPD Patients. Retrieved from: http://www.thinkcopdifferently.com/en/About-COPD/Diagnosing-COPD/Spirometric-assessment> | + | <box width classes round white centre|>{{:12028.png|}}</box| Figure 8: Mechanism of Action of Infliximab. Modified from: http://www.peterbullartstudio.co.uk/webcontent/wp-content/gallery/technical/technical30.jpg> |
| ** Effectiveness ** | ** Effectiveness ** | ||
| Infliximab is highly effective compared to other methods of treatments due to its high effectiveness and relatively low toxicity. When compared to another method of treatment, azathioprine, a purine analog working as an immunosuppressant, it has significantly better results (Colombel et al., 2010). Infliximab, seen in green on Figure 9 (replace with right number), is not more effective than a combined therapy, seen in blue. However, the combined therapy is much more toxic than the infliximab alone, therefore negates its effectiveness (Colombel et al., 2010). Furthermore, the increase in effectiveness of combined therapy is most likely due to the additive effect of using both drugs (Colombel et al., 2010). | Infliximab is highly effective compared to other methods of treatments due to its high effectiveness and relatively low toxicity. When compared to another method of treatment, azathioprine, a purine analog working as an immunosuppressant, it has significantly better results (Colombel et al., 2010). Infliximab, seen in green on Figure 9 (replace with right number), is not more effective than a combined therapy, seen in blue. However, the combined therapy is much more toxic than the infliximab alone, therefore negates its effectiveness (Colombel et al., 2010). Furthermore, the increase in effectiveness of combined therapy is most likely due to the additive effect of using both drugs (Colombel et al., 2010). | ||
| - | <box width classes round white centre|>{{:spirometry_traces_representing_healthy_patients_and_copd_patients.png|}}</box| Figure 6: Spirometry Traces Representing Healthy Patients and COPD Patients. Retrieved from: http://www.thinkcopdifferently.com/en/About-COPD/Diagnosing-COPD/Spirometric-assessment> | + | <box width classes round white centre|>{{:12029.png|}}</box| Figure 9: Comparison of Azathioprine Monotherapy, Infliximab Monotherapy, and Azathioprine and Infliximab Combined Therapy. Modified from http://www.nejm.org/doi/full/10.1056/NEJMoa0904492#t=article.> |
| **Side Effects** | **Side Effects** | ||
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| ===== Current Research ===== | ===== Current Research ===== | ||
| + | Current research is exploring the role of endogenous microbial communities in Crohn’s disease patients and healthy individuals. Researchers are concerned with dysbiosis, an imbalance in gut microbiota composition, and its association with several diseases, particularly inflammatory bowel diseases like Crohn’s. | ||
| - | <box width classes round white centre|>{{:cycle_of_weight_loss.jpg|}}</box| Figure 11: Cycle of Weight Loss. Retrieved from: http://weight.sdghealth.com/copd_and_weight_loss.html#8> | + | **Liguori et al. (2015)** |
| + | A study by Liguori et al. (2015) analyzed bacterial and fungal microbiota biodiversity, and bacterial and fungal compositions present in the colonic mucosa of both Crohn’s patients and healthy subjects. Crohn’s disease was diagnosed in these patients according to classical clinical, endoscopic, and histological parameters (Liguori et al., 2015). Patients were considered healthy if they had no history or clinical symptoms of intestinal disorders or endoscopic or histological signs of irritable bowel disease (Liguori et al., 2015). Colonic mucosa specimens of Crohn’s patients were surgically acquired during oleo-colonic resection. Diseased specimens of the right colon, in both inflamed and non-inflamed mucosa, were collected. Specimens of healthy patients were sampled during colonoscopy using standardized biopsies of the right colon (Liguori et al., 2015). Liguori et al., (2015) observed a decline in biodiversity of Crohn’s disease patients samples compared with healthy subject samples. This result was true in both active and dormant Crohn’s patients, and in inflamed and non-inflamed mucosa. In Crohn’s patients, an increase of Proteobacteria was observed with a decrease of Firmicutes and Bacteroidetes (Liguori et al., 2015). The most major differences between Crohn’s and healthy patients were observed in the Proteobacteria and Firmicutes phyla (Liguori et al., 2015). The results also revealed a significant increase of global fungus load in Crohn’s patients when compared with healthy subjects. This was observed in both inflamed and non-inflamed mucosa (Liguori et al., 2015). | ||
| + | <box width classes round white centre|>{{:screenshot_2016-12-03_12.46.29.png|}}</box| Figure 10: Differential bacterial species (left) and fungal species (right) expressed in Crohn's patients and Healthy Individuals. Modified from Liguori et al. (2015).> | ||
| - | ===== Conclusion ===== | ||
| + | <box width classes round white centre|>{{:120211.png|}}</box| Figure 11: Differential fungal taxa expressed in inflamed and non-inflamed mucosa of active cases (left) and Crohn's patients in remission (right). Modified from Liguori et al. (2015).> | ||
| + | **Hoarau et al. (2016)** | ||
| + | Another study conducted by Hoarau et al. (2016) outlines five major findings. | ||
| + | 1. Microbiotas of familial samples are distinct from those of nonfamilial samples (Hoarau et al., 2016) | ||
| + | Gut samples collected from related individuals indicated greater similarities to each other regardless of their Crohn’s disease status. This provides insight for identifying organisms linked to the disease by comparing the microbiotas within affected and unaffected family members (Hoarau et al., 2016). | ||
| - | <box width classes round white centre|>{{:action_of_anti-cholinergics.png|}}</box| Figure 14: Action of Anti-Cholinergics> | + | 2. Abundance of potentially pathogenic bacteria is increased while beneficial bacteria are decreased in CD (Hoarau et al., 2016) |
| + | An increased abundance of potentially pathogenic bacterial species, such as Escherichia coli and Serratia marcescens, were found in the samples of Crohn’s patients compared to healthy subjects. The team identified the abundance of 11 genera and 15 species that differed significantly in Crohn’s patients (Hoarau et al., 2016). | ||
| + | 3. Candida tropicalis abundance is significantly increased in CD patients (Hoarau et al., 2016) | ||
| + | Correlations between C. tropicalis abundance and anti-Saccharomyces cerevisiae antibodies (ASCA) levels were investigated because the yeasts of the genus Candida are described as immunogens for Crohn’s Disease biomarkers designated ASCAs. The ASCA level was significantly higher in Crohn’s patients than in the healthy group. C. tropicalis was also the only fungus that was positively associated with ASCA (Hoarau et al., 2016). | ||
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| + | 4. CD is associated with inter- and intrakingdom correlations (Hoarau et al., 2016) | ||
| + | Hoarau et al. (2016) found several significant associations at the genus and species levels in both bacteria and fungi. Moreover, C. tropicalis demonstrated significantly positive associations with 13 bacterial species, including E. coli and S. marcescens (Hoarau et al., 2016). | ||
| + | 5. Biofilm formation mediates interkingdom interactions in CD (Hoarau et al., 2016) | ||
| + | The analysis of a method called scanning electron microscopy (SEM) showed that biofilms formed by C. tropicalis alone comprised yeast forms while the biofilms formed by a combination of C. tropicalis and either E. coli or S. marcescens were enriched in fungal hyphae, a form of growth associated with pathogenic conditions (Hoarau et al., 2016). | ||
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| + | <box width classes round white centre|>{{:120212.png|}}</box| Figure 12: Interactions of Transmission electron microscopy analyses of biofilms formed by C. tropicalis alone or in combination with E. coli and/or S. marcescens. (A) C. tropicalis plus E. coli; (B) C. tropicalis plus S. marcescens; (C) C. tropicalis plus E. coli plus S. marcescens (bar, 0.5 m); (D) C. tropicalis plus E. coli plus S. marcescens (bar, 200 nm). Modified from Hoarau et al. (2016).> | ||
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| + | ===== Conclusion ===== | ||
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| + | A lot of research still needs to be done in order to better understand Crohn’s Disease. Genetic factors are linked with Crohn’s disease and increases the risk of diagnosis. The risk is much greater in individuals of similar familial background than those who are unrelated. Measles viral infections are also a confirmed risk factor of Crohn’s disease. Knowledge of risk may result in better preparation before diagnosis and more applicable treatments following diagnosis. Genetically susceptible individuals may engage in necessary measures to avoid triggering the disease symptoms while others may take precautions by receiving appropriate immunizations. | ||
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| + | Awareness of certain factors that exacerbate Crohn’s is valuable for disease treatment and management. Avoiding habits which jeopardize optimal health in Crohn’s patients, such as cigarette smoking and use of contraceptives, may lead to fewer flares and discomfort experienced by these individuals. Crohn’s patients may also seek alternative methods to satisfy these habitual needs. | ||
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| + | Treatment depends on the severity of each case, but medication is available for a large proportion of patients. Prednisone and infliximab/ remicade are both examples of effective pharmaceuticals prescribed to manage existing cases of Crohn’s. Current research suggest that there may be specific microbiota associated with Crohn’s disease. Recent findings on microbial communities is promising and may be pivotal point in Crohn’s disease history and treatment discovery, development, and approach. | ||
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| ===== References ===== | ===== References ===== | ||
| - | 1. Barnes, P. J. (1995). Bronchodilators: basic pharmacology. In Chronic obstructive pulmonary disease (pp. 391-417). Springer US. | + | Antoni, / C, & Braun, J. (2002). Side effects of anti-TNF therapy: Current knowledge. Clinical and Experimental Rheumatology, 20, s152-7. |
| - | 2. Bauer, J., Biolo, G., Cederholm, T., Cesari, M., Cruz-Jentoft, A. J., Morley, J. E., ... & Visvanathan, R. (2013). Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. Journal of the American Medical Directors Association, 14(8), 542-559. | + | Auphan, N., DiDonato, J.A., Rosette, C., Helmberg A, Karin M. (1995). Immunosuppression of glucocorticoids: inhibition of NF-jB activity through induction of IjB synthesis. Science. 270, 286–90. |
| - | 3. Berge, M. V., Hacken, N. H., Cohen, J., Douma, W. R., & Postma, D. S. (2011). Small Airway Disease in Asthma and COPD. Chest, 139(2), 412-423. doi:10.1378/chest.10-1210 | + | Barnes, P.J. (1998). Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci. 94, 557–72. |
| - | 4. Bourdin, A., Burgel, P., Chanez, P., Garcia, G., Perez, T., & Roche, N. (2009, September 5). Recent advances in COPD: Pathophysiology, respiratory physiology and clinical aspects, including comorbidities. European Respiratory Review, 18(114), 198-212. Doi: 10.1183/09059180.00005509. | + | Beato, M., Herrlich, P., Schutz, G. (1995). Steroid hormone receptors: many actors in search of a plot. Cell. 83, 851–857. |
| - | 5. Brug, J., Schols, A., & Mesters, I. (2004). Dietary change, nutrition education and chronic obstructive pulmonary disease. Patient education and counseling, 52(3), 249-257. | + | Colombel, J. F., Sandborn, W. J., Reinisch, W., Mantzaris, G. J., Kornbluth, A., Rachmilewitz, D., … Rutgeerts, P. (2010). Infliximab, Azathioprine, or Combination Therapy for Crohn’s Disease. New England Journal of Medicine, 362(15), 1383–1395. https://doi.org/10.1056/NEJMoa0904492 |
| - | 6. Cambach, W., Wagenaar, R. C., Koelman, T. W., van Keimpema, T., & Kemper, H. C. (1999). The long-term effects of pulmonary rehabilitation in patients with asthma and chronic obstructive pulmonary disease: a research synthesis. Archives of physical medicine and rehabilitation, 80(1), 103-111. | + | Coutinho, A.E., Chapman, K.E. (2011) The Anti-inflammatory and Immunosuppressive Effects of Glucocorticoids, recent developments and Mechanistic Insights. Mole Cell Endocrinol. 335, 2-13. |
| - | 7. Castaldi, P., et al. (2010). The COPD genetic association compendium: a comprehensive online database of COPD genetic associations. Human Molecular Genetis. 19 (3), 526-534. Doi:10.1093/hmg/ddp519 | + | Farell, R.J., Kelleher, D. (2003). Mechanisms of Steroid Actions and Resistance in Inflammation: Glucocorticoid Resistance in Inflammatory Bowel Disease. Journal of Endocrinology. 178, 339-346. |
| - | + | ||
| - | 8. Chung, K. F. (2005, June 22). The Role of Airway Smooth Muscle in the Pathogenesis of Airway Wall Remodeling in Chronic Obstructive Pulmonary Disease. Proceedings of the American Thoracic Society, 2(4), 347-354. doi:10.1513/pats.200504-028sr. | + | |
| - | 9. DeMeo, D., et al. (2009). Integration of genomic and genetic approaches implicates IREB2 as a COPD susceptibility gene. American journal of human genetics. 85 (4), 493-502. Doi:10.1016/j.ajhg.2009.09.004 | + | Hanauer, S. B., & Sandborn, W. (2001). Management of Crohn's disease in adults. The American journal of gastroenterology, 96(3), 635. |
| - | 10. Goldstein, R. S., Gort, E. H., Avendano, M. A., Stubbing, D., & Guyatt, G. H. (1994). Randomised controlled trial of respiratory rehabilitation. The Lancet,344(8934), 1394-1397. | + | Hoarau, G., Mukherjee, P. K., Gower-Rousseau, C., Hager, C., Chandra, J., Retuerto, M. A., . . . Ghannoum, M. A. (2016, September 20). Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn’s Disease. MBio, 7(5). doi:10.1128/mbio.01250-16. |
| - | + | ||
| - | 11. Hancock, D., et al. (2010). Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nature genetics. 42 (1), 45-52. Doi:10.1038/ng.500 | + | |
| - | + | ||
| - | 12. Hautamaki, R., et al. (1997). Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science (New York, N.Y.). 277 (5334), 2002-4. Doi:10.1126/science.277.5334.2002 | + | |
| - | 13. Joos, J., Pare, P., Sandford, A. (2002). Genetic risk factors for chronic obstructive pulmonary disease. Wolters Kluwer Health. 8 (2), 87-97. Doi: 2002/03/smw-09752 | + | Hollander, D., Vadheim, C. M., Brettholz, E., Petersen, G. M., Delahunty, T., & Rotter, J. I. (1986). Increased intestinal permeability in patients with Crohn's disease and their relatives: a possible etiologic factor. Annals of internal medicine, 105(6), 883-885. |
| - | 14. Ko, F. & Hui, D. (2012). Air pollution and chronic obstructive pulmonary disease. Respirology. 17 (3), 395-401. Doi: 10.1111/j.1440-1843.2011.02112.x | + | Irving, P. M., & Gibson, P. R. (2008). Infections and IBD. Nature Clinical Practice Gastroenterology & Hepatology, 5(1), 18-27. |
| - | 15. MacNee, W. (2006, May 20). ABC of chronic obstructive pulmonary disease: Pathology, pathogenesis, and pathophysiology. Bmj, 332(7551), 1202-1204. doi:10.1136/bmj.332.7551.1202. | + | Janssen Biotech. (2016). How REMICADE® Works | REMICADE® (infliximab). Retrieved from http://www.remicade.com/crohns-disease/how-remicade-works. |
| - | 16. Matheson, M., et al. (2005). Biological dust exposure in the workplace is a risk factor for chronic obstructive pulmonary disease. Thorax. 60 (8), 645-51. Doi: 10.1136/thx.2004.035170 | + | Jobin, C., Sartor, R.B. (2000). NF-jB signaling proteins as therapeutic targets for inflammatory bowel diseases. Inflamm Bowel Dis. 6, 206–13. |
| - | 17. Paknikar S. (2013). Increased Airway Resistance in COPD Occurs Due to Loss or Narrowing of Small Airways. http://www.medindia.net/news/healthinfocus/increased-airway-resistance-in-copd-occurs-due-to-loss-or-narrowing-of-small-airways-92858-1.htm | + | Kirman, I., Whelan, R. L., & Nielsen, O. H. (2004). Infliximab: mechanism of action beyond TNF-alpha neutralization in inflammatory bowel disease. European Journal of Gastroenterology & Hepatology, 16(7), 639–41. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15201575 |
| - | 18. Pendas, A., et al. (1996). Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3. Genomics. 37 (2), 266-8. Doi: 10.1006/geno.1996.0557 | + | Koletzko, S., Sherman, P., Corey, M., Griffiths, A., & Smith, C. (1989). Role of infant feeding practices in development of Crohn's disease in childhood. BMJ: British Medical Journal, 298(6688), 1617. |
| - | 19. Pillai, S., et al. (2009). A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS genetics. 5 (3). Doi: 10.1371/journal.pgen.1000421 | + | Liguori, G., Lamas, B., Richard, M. L., Brandi, G., Costa, G. D., Hoffmann, T. W., . . . Sokol, H. (2015). Fungal Dysbiosis in Mucosa-associated Microbiota of Crohn’s Disease Patients. ECCOJC Journal of Crohn's and Colitis, 10(3), 296-305. doi:10.1093/ecco-jcc/jjv209 |
| - | 20. Ries, A. L., & Squier, H. C. (1996). The team concept in pulmonary rehabilitation. Lung Biology in Health and Disease, 91, 55-66. | + | Lügering, A., Schmidt, M., Lügering, N., Pauels, H. G., Domschke, W., & Kucharzik, T. (2001). Infliximab induces apoptosis in monocytes from patients with chronic active Crohn’s disease by using a caspase-dependent pathway. Gastroenterology, 121(5), 1145–57. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11677207 |
| - | 21. Ries, A. L., Bauldoff, G. S., Carlin, B. W., Casaburi, R., Emery, C. F., Mahler, D. A., ... & Herrerias, C. (2007). Pulmonary rehabilitation: joint ACCP/AACVPR evidence-based clinical practice guidelines. CHEST Journal,131(5_suppl), 4S-42S. | + | Malchow, H., Ewe, K., Brandes, J.W., et al. (1984) European cooperative Crohn’s disease study (ECCDS): results of drug treatment. Gastroenterology. 86, 249–66. |
| + | Probert, C. S., Jayanthi, V., Hughes, A. O., Thompson, J. R., Wicks, A. C., & Mayberry, J. F. (1993). Prevalence and family risk of ulcerative colitis and Crohn's disease: an epidemiological study among Europeans and south Asians in Leicestershire. Gut, 34(11), 1547-1551. | ||
| - | 22. Rossi, A., Khirani, S., & Cazzola, M. (2008). Long-acting β2-agonists (LABA) in chronic obstructive pulmonary disease: efficacy and safety. International Journal of Chronic Obstructive Pulmonary Disease, 3(4), 521–529. | + | Scheinman RI, Cogwell PC, Lofquist AK & Baldwin Jr AS (1995) Role of transcriptional activation of I_B_ in mediation of immunosuppression by glucocorticoids. Science; 270: 283–286. |
| - | 23. Schols, A. M., Slangen, J. O. S., Volovics, L., & Wouters, E. F. (1998). Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine, 157(6), 1791-1797. | + | Thompson, N. P., Pounder, R. E., Wakefield, A. J., & Montgomery, S. M. (1995). Is measles vaccination a risk factor for inflammatory bowel disease?. The Lancet, 345(8957), 1071-1074. |
| - | + | ||
| - | 24. Shim, C. (1989). Response to bronchodilators. Clinics in chest medicine, 10(2), 155-164. | + | |
| - | + | ||
| - | 25. Smith, C. & Harrison, D. (1997). Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema. The Lancet. 350 (9078), 630-633. Doi: 10.1016/S0140-6736(96)08061-0 | + | |
| - | 26. Takeda (2012). Pathophysiology of COPD. http://www.thinkcopdifferently.com/About%20COPD/What%20is%20COPD/Pathophysiology%20of%20COPD.aspx | + | Timmer, A., Sutherland, L. R., & Martin, F. (1998). Oral contraceptive use and smoking are risk factors for relapse in Crohn's disease. Gastroenterology, 114(6), 1143-1150. |
| - | + | ||
| - | 27. Tashkin, D. P., & Fabbri, L. M. (2010). Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents. Respiratory research, 11(1), 1. | + | |
| - | 28. Tests for COPD. (n.d.). NHS. Retrieved from http://www.nhs.uk/Conditions/Chronic-obstructive-pulmonary-disease/Pages/Diagnosis.aspx | + | Van Deventer, S. J. H. (2001). Transmembrane TNF-α, induction of apoptosis, and the efficacy of TNF-targeting therapies in Crohn’s disease. Gastroenterology, 121(5), 1242–1246. https://doi.org/10.1053/gast.2001.29035 |
| + | |||
| + | Wakefield, A. J., Sawyerr, A. M., Hudson, M., Dhillon, A. P., & Pounder, R. E. (1991). Smoking, the oral contraceptive pill, and Crohn's disease. Digesive diseases and sciences. 36, 1147-1150. | ||
| - | 29. Van Noord, J. A., Aumann, J. L., Janssens, E., Smeets, J. J., Verhaert, J., Disse, B., ... & Cornelissen, P. J. G. (2005). Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD. European Respiratory Journal, 26(2), 214-222. | + | Wild, G.E., Waschke, K.A., Bitton, A., Thomson, A.B.R. (2003). The Mechanisms of Prednisone Inhibition of Inflammation in Disease In Crohn’s Disease Involve Changes in Intestinal Permeability, Mucosal TNF alpha Production and Nuclear factor kappa B expression. Ailment Pharmacol Theory. 18, 309-317. |
| - | + | ||
| - | 30. Willemse, B. W. M., Ten Hacken, N. H. T., Rutgers, B., Lesman-Leegte, I. G. A. T., Postma, D. S., & Timens, W. (2005). Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers. European Respiratory Journal, 26(5), 835-845. | + | |
| - | + | ||
| - | 31. Willemse, B. W. M., Ten Hacken, N. H. T., Rutgers, B., Lesman-Leegte, I. G. A. T., Timens, W., & Postma, D. S. (2004). Smoking cessation improves both direct and indirect airway hyperresponsiveness in COPD. European respiratory journal, 24(3), 391-396. | + | |
