Related Articles

Chronic rhinosinusitis (CRS) is a group of multifactorial diseases characterized by inflammation of the mucosa of the nose and paranasal sinuses with a history of at least 12 weeks of persistent symptoms despite maximal medical therapy. The precise role played by infection and immunoglobin E (IgE)-mediated hypersensitivity remains unclear. Diagnosis of CRS is based upon medical history, nasal endoscopy and computed tomography scan of the sinuses. The CRS with polyps visible in the middle meatus must be distinguished from the CRS without polyps. Based on the current knowledge about the pathogenesis of CRS, it is admitted that an optimal medical treatment must consider all favorizing factors and control efficaciously the inflammation process. In case of failure of medical treatment, endoscopic sinus surgery should be proposed. However, some well-validated data and scientific evidences are missing, even for the most frequently used medications. After a review of the actual definitions and classifications, a short description of the current knowledge about pathogenesis of CRS is provided in order to justify the actual therapeutic rationales and identify the needs for an effective treatment of CRS.

Background

Chronic rhinosinusitis (CRS) is an inflammatory condition of the nasal airway and paranasal sinuses that can broadly be classified into Chronic rhinosinusitis with Nasal Polyps (CRSwNP) and Chronic rhinosinusitis without Nasal Polyps (CRSsNP). The relationship between CRS and atopy to inhalant allergens remains unclear. We sought to examine the presence of atopy in patients failing medical therapy for both types of CRS.

Objective

To analyze the frequency and distribution of allergen sensitivity in patients failing medical therapy for CRSwNP and CRSsNP in comparison to rhinitis patients without CRS and the general population.

Methods

A prospectively collected database of 334 consecutive CRS patients who had surgery after failing maximal medical therapy was queried to identify those who met inclusion criteria: a Sinus Computed Tomography(CT), an endoscopy consistent with CRS and skin-prick testing with 24 common inhalant allergens in 8 classes at our institution (n=125). Additionally, data from these CRS patients were compared to a group of 50 patients diagnosed with rhinitis who had similar symptoms but radiologically normal CT scans, as well as published normative population skin prick testing data obtained from the National Health and Nutrition Examination Study III (NHANES III). The relationship between atopy, as assessed by the frequency of skin test positivity, and radiological disease severity was assessed for several allergen classes in CRSwNP, CRSsNP and rhinitis patients.

Results

One or more positive skin results were observed in 103/125 (82.4%) CRS patients who underwent surgery- a prevalence significantly higher than that found in the NHANES III study (p<0.05) but not different from the rhinitis control group (36/50 -72.0 %). The most prevalent positive skin test results were to dust mites and ragweed in CRSwNP, CRSsNP and rhinitis patients. Comparing these three patient groups, there were no significant differences in the rates of positive skin test results to any single allergen. However, the median number of skin test positive results was higher in CRSwNP patients compared to CRSsNP and rhinitis patients. Consistent with other studies, we found that CRSwNP patients were more likely to be male and have concurrent asthma.

Conclusions

In our series of patients failing medical therapy for CRS, we found higher rates of atopy compared with the general population but not compared with rhinitis patients. CRSwNP patients with medically refractory sinusitis were more likely to have multiple positive skin tests and asthma as compared to the general population or patients with either CRSsNP or rhinitis. Host barrier dysfunction may play a role in enabling multisensitization.

This study was designed to assess the efficacy of functional endoscopic sinus surgery (FESS) in chronic rhinosinusitis (CRS) patients with minimal radiological findings, and based on one centre, prospective randomized controlled study, conducted in the Department of Otorhinolaryngology, Lady Hardinge Medical College, New Delhi. All the CRS out-patients (>18 years) refractory to 3 weeks of medical therapy were radiologically evaluated with computerised tomographic scan (CT) of nose and paranasal sinuses. These patients were grouped based on CT scoring (Lund Mackay staging system): group A (CT score 0–6) and group B (CT score 7–24); with 35 patients in each group. All the patients underwent FESS using Messerklinger technique. Symptom scoring of all the patients was done using visual analog scale preoperatively and postoperatively at 1-, 3-, 6- and 12-month follow-up. CRS patients with minimal evidence of disease on CT showed statistically significant improvement in symptom scores after FESS. There was no significant difference noted in the overall symptom score improvement as well as for improvement in specific symptoms in both the groups. Further, there was no correlation between the pre-operative symptoms and CT scores. A good subjective outcome in terms of symptom improvement can be obtained with FESS in patients with CRS with minimal evidence of disease on CT.

Aspirin-exacerbated respiratory disease (AERD) refers to aspirin sensitivity, chronic rhinosinusitis (CRS), nasal polyposis, asthma, eosinophil inflammation in the upper and lower airways, urticaria, angioedema, and anaphylaxis following the ingestion of NSAIDs. Epidemiologic and pathophysiological links between these diseases are established. The precise pathogenesis remains less defined, even though there is some progress in the understanding of several molecular mechanisms. Nevertheless, these combinations of diseases in patients classified by AERD constitute a fatal combination and may be difficult to treat with standard medical and surgical interventions. This paper reviews in brief the epidemiology, clinical features, diagnosis, molecular pathogenesis, and specific therapies of patients classified by AERD and postulates future attempts to gain new insights into this disease.

BACKGROUND:

Autoimmune hepatitis (AIH) is a chronic inflammatory disease that is successfully treated with prednisone and/or azathioprine immunosuppressive therapy in 70% to 80% of patients. The remaining patients are intolerant or refractory to these standard medications. Budesonide, a synthetic glucocorticoid, undergoes a high degree of first-pass metabolism, reducing its systemic bioavailability, and has a 15-fold greater affinity for the glucocorticoid receptor than prednisolone. Budesonide may be a potentially useful systemic steroid-sparing immunosuppressive agent in the treatment of AIH.

OBJECTIVE:

To review the Canadian experience using budesonide to treat AIH.

METHODS:

Patients with AIH currently or previously treated with budesonide were identified through the Canadian Association for the Study of the Liver membership. Data were collected regarding their clinical and treatment history.

RESULTS:

A total of nine patients were identified. All patients were female, with an average age of 39 years (range 12 to 66 years). The indications for budesonide were adverse side effects of prednisone in two patients, noncompliance with prednisone and azathioprine in one patient and intolerance to azathioprine resulting in prednisone dependence in the remaining six patients. Patients were treated in doses ranging from 9 mg daily to 3 mg every other day for 24 weeks to eight years. Seven of nine patients had a complete response, defined as sustained normalization of the aminotransferase levels. The remaining two patients were classified as nonresponders (less than a 50% reduction in pretreatment aminotransferase levels).

CONCLUSIONS:

In Canada, budesonide has been successfully used in seven of nine patients with autoimmune hepatitis who were either intolerant to prednisone and azathioprine or prednisone-dependent. No adverse effects were reported with budesonide. Budesonide is potentially a valuable treatment option for AIH patients refractory or intolerant to standard therapy, and is deserving of further study.

SUMMARY

The objective of the present study was to compare the efficacy of functional endoscopic dilatation sinus surgery (FEDS) with functional endoscopic sinus surgery (FESS) in treatment of chronic rhinosinusitis in patients who failed medical therapy. We enrolled 24 patients suffering with chronic rhinosinusitis, who failed medical treatment and were proceeding to surgery, in a prospective, randomized controlled pilot study carried out between January and December 2008 following ethical committee approval. All patients completed sino-nasal outcome test (SNOT)-20 questionnaires and underwent saccharine test preoperatively and 24 weeks post operatively. Only trained surgeons performed surgery. The SNOT-20 questionnaire and saccharine clearance time (SCT) were used to measure outcomes. The SNOT-20 scores for both patient groups showed similar, consistent symptomatic improvement compared with baseline measures. SCT was reduced in both groups. No significant post-operative complications were recorded in either group. No patient in the FEDS group had any bleeding, and all were ready for discharge within hours of the procedure. Thus, FEDS is as effective as FESS in treatment of chronic rhinosinusitis. It is can be considered an additional tool in endoscopic surgery and has the potential to be undertaken as a day procedure.

Background

Abnormalities in host mucosal immunity exist in chronic rhinosinusitis with nasal polyps (CRSwNPs), but it is unclear whether this is a cause or an effect of the eosinophilic inflammation and frequent microbial colonization that characterizes the disease. Sinonasal epithelial cells (SNECs) are critical participants in healthy antimicrobial innate immune defense. They also can promote Th2 inflammation with various mediators, including interleukin (IL)-33, which induces T helper cells to produce Th2 cytokines.

Methods

CRSwNP SNECs were obtained during sinus surgery and stored. Patients were subsequently classified as either treatment responsive or treatment recalcitrant, based on long-term outcomes of medical and surgical therapy. Epithelial cells from these patients were grown in air–liquid interface (ALI) culture and treated with IL-13, as well as the bacteria-associated molecule, CpG. Expression of IL-33 mRNA was determined by real-time polymerase chain reaction.

Results

Recalcitrant CRSwNP epithelial cells had increased baseline expression of IL-33 compared with responsive CRSwNPs, which was further increased by 24-hour exposure to CpG. Treatment-responsive epithelial cells were not induced by CpG to express IL-33. Prolonged treatment with IL-13 during differentiation at the ALI diminished the baseline expression of IL-33 and prevented the subsequent induction of IL-33 by CpG.

Conclusion

Mucosal innate immunity likely plays an important role in CRSwNP pathogenesis. A definitive link between infectious triggers and the development of Th2 inflammation has been elusive. We have found constitutive IL-33 expression by SNECs in recalcitrant CRSwNPs, which can be further induced by a bacteria-associated molecular pattern. Dysregulated epithelial cell immune interactions between host and environment may contribute to Th2 inflammation in CRSwNPs.

Background

Recent literature has indicated the feasibility of microarray analysis in the characterization of chronic sinusitis. We hypothesized that previously unexplored inflammatory mechanisms would be involved in the pathophysiology of noneosinophilic chronic rhinosinusitis with nasal polyps (NE-CRSwNP) and that this technology could be used to identify the gene expression of these novel and previously known mediators.

Methods

Patients with CRSwNP failing medical therapy were prospectively enrolled and NP tissue was removed at time of surgery. NE-CRSwNP was diagnosed based on clinical parameters including absence of allergic disease and confirmed with histopathology showing lack of eosinophilic infiltration. Messenger RNA (mRNA) transcripts extracted from study and control patients were then subjected to microarray analysis using Affymatrix based chips. Validation of findings was then confirmed via quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results

Microarray analysis revealed activation of pathways involved in antigen presentation, cellular movement, hematopoiesis, carcinogenesis, apoptosis, and cell signaling. Previously unexplored genes of interest were identified and their differential regulation was validated via qRT-PCR. Our data showed up-regulation of innate inflammation genes (IL-6, IL-8, and monocyte chemoattractant protein 1), hypoxia-induced inflammation 1α, and fibrosis (tenascin) and lack of up-regulation of genes associated with allergic, eosinophilic inflammation (IL-4 and IL-13). Additionally, the genes for CXCL1 and autocrine motility factor receptor were novelly identified to be up-regulated

Conclusion

This study explores the utility of gene microarray technology in identifying unexplored targets of immune dysregulation in NE-CRSwNP. Furthermore, the data characterize the immunologic profile of NE-CRSwNP as it differs from other forms of CRSwNP, in particular, those known to be associated with eosinophilic inflammation.

Background

Specific antibody deficiency may predispose patients to recurrent respiratory tract infections. There is limited literature assessing specific antibody deficiency in chronic rhinosinusitis (CRS). This study evaluated the role of specific antibody deficiency in patients with CRS who have failed medical therapy.

Methods

We performed a retrospective chart review of patients with CRS who underwent functional endoscopic sinus surgery and had prior assessment for humoral immunodeficiency. Each patient’s record was reviewed for serum quantitative immunoglobulin G (IgG) and IgA and anti–Streptococcus pneumoniae antibody titers measured at baseline and 6 weeks postvaccination with the 23-valent unconjugated pneumococcal vaccine. Clinical characteristics, including asthma, atopy, and nasal polyps, were recorded.

Results

Of the 129 CRS patients who met inclusion criteria, 93 (72%) had low baseline antipneumococcal titers. Fifteen (11.6%) patients were diagnosed with specific antibody deficiency based on an inadequate response to the pneumococcal polysaccharide vaccine. The group of patients with specific antibody deficiency had significantly lower serum IgA levels when compared with those patients with normal preimmunization titers (138 ± 67.3 versus 330 ± 356; p < 0.05). Patients with specific antibody deficiency had a significantly lower number of preimmunization protective antipneumococcal titers when compared with vaccine responders (1.41 versus 2.72; p < 0.0005).

Conclusion

This retrospective study indicates that patients with medically refractory CRS may have a high prevalence of low preimmunization antipneumococcal titers and specific antibody deficiency. Furthermore, lower serum IgA levels identified in these specific antibody deficiency patients suggests that a prospective study to further characterize this relationship is warranted.

Background

Viral and bacterial infections can modulate the ongoing inflammation in both upper and lower airways of patients with chronic rhinosinusitis with nasal polyps (CRS/NP) and asthma. It was not clear if the protective immune response to pathogens may differ depending on the disease severity.

Object: To compare serum IgG immune response against respiratory pathogens in patients with chronic airway disease (CRS/NP and asthma) with and without sensitivity to aspirin, and to refer the sensitization to severity of chronic rhinosinusitis.

Methods

We recruited 73 patients with CRS/NP and asthma with (43 patients) and without (30 patients) hypersensitivity to aspirin. The extent of mucosal hypertrophy in paranasal sinuses was assessed by CT scans and the sense of smell was valuated with “sniffing smell” test. Serum IgG immunoglobulin levels against respiratory pathogens: Respiratory Syncytial Virus (RSV), Adenowirus (ADV), Parainfluenza virus (PIV) and Mycoplasma pneumoniae were determined by ELISA.

Results

Patients with ASA-hypersensitivity had history of significantly more nasal polypectomies (P = 0.002), lower smell test score (P = 0.03) and higher mean paranasal CT score (P = 0.03) as compared to ASA-tolerant patients, reflecting higher severity of the upper airway disease. The percentage of positive serological testing to respiratory pathogens was very high in the whole group of patients with CRS/NP and asthma (RSV, 95.8%; ADV, 95.9%; PIV, 84.9% and Mycoplasma pneumonieae, 100% patients) without any difference between ASA-sensitive and ASA-tolerant subjects. Patients with ASA-sensitivity had significantly lower concentrations of PIV- specific IgG (mean 188.67 ± 34.46 U/mL versus 207.56 ± 30.036 U/mL; P < 0.04) as compared to ASA-tolerant subjects. There was a significant trend (P < 0.048) for lower PIV–specific IgG concentrations with increased number of polypectomies. No correlation of IgG immunoglobulin concentrations for other pathogens with the number of polypectomies, paranasal sinuses CT score or presences of smell were observed.

Conclusions

Patients with CRS/NP and asthma had high frequency of IgG immunoglobulin against common respiratory pathogens. Serum IgG immune response to paramyxoviruses may be related to the recurrence of nasal polyps and the presence of aspirin sensitivity.

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract. While a cure remains elusive, both can be treated with medications that induce and maintain remission. With the recent advent of therapies that inhibit tumor necrosis factor (TNF) alpha the overlap in medical therapies for UC and CD has become greater. Although 5-ASA agents have been a mainstay in the treatment of both CD and UC, the data for their efficacy in patients with CD, particularly as maintenance therapy, are equivocal. Antibiotics may have a limited role in the treatment of colonic CD. Steroids continue to be the first choice to treat active disease not responsive to other more conservative therapy; non-systemic steroids such as oral and rectal budesonide for ileal and right-sided CD and distal UC respectively are also effective in mild-moderate disease. 6-mercaptopurine (6-MP) and its prodrug azathioprine are steroid-sparing immunomodulators effective in the maintenance of remission of both CD and UC, while methotrexate may be used in both induction and maintenance of CD. Infliximab and adalimumab are anti-TNF agents approved in the US and Europe for the treatment of Crohn's disease, and infliximab is also approved for the treatment of UC.

The surgical management of chronic rhinosinusitis has evolved considerably in the last decade. We currently have a more refined understanding of the various disease entities that make up the generic diagnosis of chronic rhinosinusitis. This has led to the development of more sophisticated medical and surgical therapy for the different entities. Failure of maximal medical therapy leads to the consideration of surgical intervention with the general intent of improving the patient's quality of life. Recent technical innovations such as mucosa-preserving instrumentation and image guidance systems for intraoperative localization have given surgeons increased confidence and enabled more complete and effective surgical management of chronic rhinosinusitis, particularly in revision surgeries or in the presence of distorted landmarks. Improved packing materials and refinement of postoperative care are active areas of investigation and innovation that, it is hoped, will also translate into improved patient care.

Background

Matrix metalloproteinases (MMPs) are key enzymes responsible for extracellular matrix degradation contributing to the progressive histological changes seen in lower airway disease, including asthma. MMP-9 and TIMP-1 have also shown some role in the pathogenesis of chronic rhinosinusitis (CRS) and nasal polyposis (NP).

Objective

We aim to determine variability in expression of MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in sinus tissue from distinct patient populations presenting with nasal polyposis.

Methods

The expression of MMP-9 and TIMP-1 was investigated in nasal polyp tissue from 6 aspirin-sensitive (AS) and 6 aspirin-tolerant (AT) patients undergoing endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis (CRSwNP). Sinus mucosa from 6 patients with chronic rhinosinusitis without nasal polyposis (CRSsNP) was used as control. The MMP-9 and TIMP-1 expression was measured using immunofluorescence technique and graded using manual and computerized methods.

Results

Expression of TIMP-1 was significantly reduced in the AS group when compared with both the AT and CRSsNP (control) groups (P < .001). The MMP-9/TIMP-1 ratio was significantly increased in the AS group when compared with other patient groups (P < .001). The MMP- 9 expression was similar between study and control groups.

Conclusion

These results support the importance of MMP-9 and TIMP-1 expression in nasal polyp formation. The decreased expression of TIMP-1 in AS patients may promote the effects of MMP-9 expression and thus contribute to tissue remodeling and inflammatory changes. This finding may lead to further understanding of disease severity and resistance to treatment in this group of patients, as well as the pathogenesis of nasal polyps.

Background

It is said that the chronic rhinosinusitis influences the lower respiratory airway and there is a report that a tendency to increase the eosinophilic rhinosinusitis later, but they are still unknown.

Methods

We divided the chronic rhinosinusitis patients with the adaptation of the operation into 4 groups and exaed whether there was a difference in the respiratory function, exhaled NO, and the number of the blood eosinophil.

Object

29 patients with chronic rhinosinusitis who planned the endonasal sinus surgery.

Results

Comparing these 4 groups, it was the worst on the respiratory function (one second rate) in the group with nasal polyps and without nasal allergy. It was recognized the connection between the respiratory function and the presence of the nasal polyps. It was possible that the exhaled NO became the index to the lower airway inflammation.

Conclusions

We classified the chronic rhinosinusitis and evaluated the lower airway function. It helps the pathologic understanding of the chronic rhinosinusitis. And it leads to understand of the influence on the lower airway inflammation.

We report a case of eosinophilic chronic rhinosinusitis (ECRS) associated with optic neuropathy. The visual acuity in the right eye was suddenly reduced to no light perception on awakening in the morning. Fundus examination of both eyes on the same day showed no remarkable changes. Emergency computed tomography showed pan-sinusitis bilaterally and a partial defect of the sphenoid bone on the right side. From the clinical findings, the case was diagnosed as optic neuropathy associated with chronic sinusitis. Endoscopic sinus surgery (ESS) was performed on the same day, and all of the major sinuses were found to be filled with highly viscous fluid. Part of the optic canal had a defect probably due to inflammatory invasion from the adjacent sphenoid bone. Steroid therapy was started immediately postoperatively. Histopathological examination of excised polyps showed that numerous eosinophils had invaded the polyps but no hyphae were present. The patient reported that he had bronchial asthma and had had nasal polypectomy. Six months after the ESS and steroid therapy, the patient had a recurrence of the sinusitis. At that time, laboratory examination showed an elevation of total IgE and eosinophil numbers. From the clinical findings and course, this case was diagnosed as ECRS accompanied by optic neuropathy. Although ECRS rarely has ocular complications, the inflammation can spread and the optic nerve can be affected.

Staphylococcus aureus, a primary source of bacterial superantigen (SAg), is known to colonize the human respiratory tract and has been implicated in airway inflammation. Studies have documented a role for SAgs in respiratory disorders, such as nasal polyps, chronic obstructive pulmonary disease, chronic rhinosinusitis, and asthma. However, cellular and molecular mediators involved in SAg-mediated pulmonary disease have not been clearly identified. In this study, we investigated the effect of intranasal staphylococcal enterotoxin A (SEA) exposure on murine lung. The pathological features in the lung resulting from SEA exposure had characteristics of both obstructive and restrictive pulmonary disorders. There was also an increase in bronchoalveolar lavage protein concentration and cellularity following SEA challenge. Massive CD8+Vβ3+ T cell accumulation observed in the lung was dependent on CD4 T cell help, both for recruitment and for IFN-γ synthesis. The primary source of IFN-γ synthesis was CD8 T cells, and depletion of these cells abrogated disease. IFN-γ deficiency also prevented SEA-mediated disease, and this was by enhancing early recruitment of neutrophils as detected in the bronchoalveolar lavage. Thus, IFN-γ appeared to selectively aid the recruitment of T cells to the lungs while preventing the neutrophil accumulation. Therefore, our results show that IFN-γ-producing CD8 T cells mediated pulmonary alveolitis and inflammation, which were dependent upon CD4 T cells for their recruitment to the lung.

Background

Non-allergic rhinopathy (NAR), formerly known as vasomotor rhinitis, is a non-allergic and non-infectious chronic disease that is accompanied by nasal hyperemia, rhinorrhea, and no increase in the number of eosinophils. Although the medications for NAR, including intranasal corticosteroids and intranasal antihistamine, have been used in clinical practice, given the relative paucity of effective therapy with available medications, alternative non-pharmacologic treatments could play an important role in treating NAR. Acupuncture treatment is representative potential alternative therapy for the treatment of various diseases, including rhinitis. Therefore, the objective of this study was to evaluate the efficacy of pricking blood at Neiyingxiang (ExHN 9) relative to acupuncture treatment at Waiyingxiang (LI 20) in patients with NAR.

Methods/Design

A randomized, parallel-group, controlled, assessor single-blinded, trial will be conducted. Fifty participants with NAR will be randomized into one of two groups: either the control group with acpuncture treatment at LI 20 or the experimental group with pricking blood at ExHN 9. After randomization, a total of three sessions of treatment will be performed once a week in both groups. The total nasal symptom score (TNSS) and the Mini-Rhinoconjunctivitis Quality-of-Life Questionnaire (MiniRQLQ) at baseline and the end of the trial will be used to evaluate the efficacy of each treatment.

Discussion

This study will be the first randomized trial to evaluate the efficacy of pricking blood for the treatment of NAR. The results of this study will help establish an alternative approach for treating patients with NAR that do not respond to Western medication.

Trial registration

The trial was registered with the Clinical Research Information Service (CRiS), Republic of Korea: KCT0000195.

Objective

Determine the time interval over which quality-of-life (QOL) outcomes stabilize after endoscopic sinus surgery (ESS).

Study Design

Multi-institutional, longitudinal cohort.

Setting

Tertiary rhinology centers.

Subjects and Methods

Adults with chronic rhinosinusitis from three medical centers were asked to provide responses to the Rhinosinusitis Disability Index (RSDI) and the Chronic Sinusitis Survey (CSS) at baseline and 6 months, 12 months, and 20 months after endoscopic sinus surgery. Repeated measures and post hoc analyses were used to compare QOL scores between follow-up time points. Subgroup analyses were done in a similar fashion for patients with and without nasal polyposis, asthma, allergies, acetylsalicylic acid intolerance, depression, and prior sinus surgery

Results

A total of 127 patients provided complete follow-up data for all three time points. Improvement in QOL scores was seen at 6 months after surgery for both the RSDI and CSS instruments. When comparing changes in mean QOL scores between all follow-up time points, there were no significant differences in either RSDI or CSS total scores (all p ≥ 0.853) or subscale scores (all p ≥ 0.251) between 6, 12, and 20 months. Each individual subgroup demonstrated stable QOL scores between 6 and 20 months follow-up, including patients with polyposis and those with ASA intolerance (all p ≥ 0.275).

Conclusion

At a cohort level, improvements in QOL after ESS do not appear to change between 6 and 20 months. Clinical trial designs incorporating QOL outcomes after ESS should consider the six month time frame as an appropriate primary endpoint.

Abstract

Rhinosinusitis is a significant health problem, causing significant morbidity and resulting in considerable financial cost. Some patients suffer persistent or recurrent symptoms despite receiving optimal medical and surgical treatment. Rhinosinusitis can be acute or chronic, acute often due to viral or bacterial infections and chronic which is classified into chronic with nasal polyposids or chronic rhinosinusitis without nasal polyposis. The disease affects the quality of life significantly and presents a significant burden on health costs globally. The anatomical linkage of the nose with the paranasal sinuses facilitates a common pathology in both organs. Chronic rhinosinusitis (CRS) has heterogeneous origins, including viruses, bacteria, fungal infections, anatomical abnormalities, polyposis, and aspirin sensitivity. Other conditions such as human immunodeficiency virus acquired immunodeficiency and cystic fibrosis may also be predisposing factors. Nasal polyposis is often associated with increased numbers of Th2 lymphocytes, fibroblasts, goblet cells, mast cells, and eosinophils, with upregulation of IL-13 and the release of specific IgE to staphylococcal enterotoxins. There is recent evidence that antibiotic treatment may not be as effective as higher doses of intranasal steroids in acute uncomplicated rhinosinusitis, especially in those with allergic disease. The broad inflammatory basis of the pathology of CRS also reveals a cellular infiltrate theoretically suppressed by intranasal corticosteroids. This has been confirmed in recent clinical studies of CRS with or without polyps. A treatment approach based on such studies reported in the European Position Paper on Rhinosinusitis guidelines and a guideline summary are presented. The current review represents the proceedings of a session (3 talks) by the authors at the first Middle East-Asia Allergy, Asthma, Immunology Congress in 2009.

Nasal polyposis are common presentations in patients of chronic rhinosinusitis and are considered to be associated with more severe forms of disease with poor treatment outcome. The presentation and treatment outcome after endoscopic sinus surgery in patients of chronic rhinosinusitis and nasal polyposis have been analysed in this study. A prospective analysis of 90 patients of chronic rhinosinusitis who were classified into two groups depending on presence and absence of nasal polyps was performed in the study. The two groups were evaluated using subjective (patient complaints) and objective (computed tomography scan and endoscopy scores) criteria. Preoperative data were compared with data obtained 12 months post endoscopic sinus surgery. The study included 38 patients of chronic rhinosinusitis and 52 patients of nasal polyps. The patients of nasal polyp group presented with increased severity of symptoms of nasal blockage, nasal discharge and reduced sense of smell as compared to the chronic rhinosinusitis group who had significantly higher presentation of headache and facial pain. The preoperative CT scan revealed significantly higher bilateral disease with increased involvement of multiple sinuses in nasal polyp group. Post endoscopic sinus surgery both the groups showed significant improvement in their symptoms with the nasal polyp group demonstrating reduction in improvement on 1 year follow up. In our study we have found the patients with chronic rhinosinusitis and nasal polyp have varied severity of symptoms with the nasal polyp group having higher nasal symptoms and increased severity as compared to chronic rhinosinusitis group. Though the universal rationale of management by adequate drainage and ventilation of sinus is similar in both groups, there is a reduction in both objective and subjective scores during 1 year follow up in the nasal polyp group.

Schizophrenia is a chronic mental disorder generally treated with antipsychotic medication. However, non-adherence and partial adherence to antipsychotic medication treatment is common and long-acting injectable “depot” preparations of antipsychotic medications have been used as an alternative to oral medication therapy for patients for whom adherence is a clinically significant problem, as well as for the sake of convenience and in response to patient preference. Olanzapine long-acting injection (OLAI) is a new treatment option and has been approved by several regulatory agencies for the treatment of schizophrenia. OLAI is a crystalline salt formulation of olanzapine and pamoic acid. Efficacy was established in 2 double-blind randomized clinical trials of OLAI for the treatment of acute schizophrenia and for the maintenance of response. The therapeutic OLAI dosages are 150 mg q2 weeks, 210 mg q2 weeks, 300 mg q2 weeks or q4 weeks, and 405 mg q4 weeks, administered by deep intramuscular gluteal injection with a 19-gauge needle. Injection volume ranges from 1 to 2.7 mL. OLAI has essentially the same general tolerability as that of oral olanzapine; however with the depot there is the additional risk of a post-injection delirium sedation syndrome occurring at a rate of 0.07% of injections, requiring a risk management plan that includes observing the patient for 3 hours post injection.

Background

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may play an important role in both inflammation and remodeling of nasal polyposis. The aim of the current study was to compare the expression levels of MMPs and TIMP-1 between nasal mucosa and polyps, and to evaluate the effect of corticosteroid treatment in their expression in nasal polyps.

Methods

Nasal mucosa (NM, n = 12) were obtained from patients undergoing nasal corrective surgery while nasal polyp biopsies (NP, n = 33) were obtained from patients before (week 0) and after 2 (week 2) and 12 (week 12) weeks of corticoisteroid treatment (oral prednisone for 2 weeks and intranasal budesonide for 12 weeks). Matrix metalloproteases (MMP-1, MMP-2, MMP-7, MMP-9) and tissue inhibitor of metalloproteinases type 1 (TIMP-1) expression was evaluated by immunohistochemistry in tissue structural cells (epithelium, glands, vessels) and eosinophils.

Results

MMP and TIMP-1 expression were found in the epithelium, glands, vessels (in both NM and NP), and in eosinophils (only in NP). Expression of MMP-7 in epithelium (34% of tissues) and MMP-9 (19%) in glands was lower (P < 0.05) in NP than in NM (78 and 67%, respectively). Corticoisteroid treatment reduced tissue eosinophilia (Eos/5 fields) at week 2 (8.0 ± 2.9, P = 0.001) and week 12 (10.0 ± 2.3, P < 0.003) compared to week 0 (25.5 ± 8.4); and also decreased the expression of MMPs and TIMP-1 in eosinophils at week 2 and week 12 compared to week 0 (P < 0.05). In the epithelium, corticosteroids increased MMP-7 and TIMP-1 at week 2 and week 12, while decreased MMP-9 at week 12 (P < 0.05). In vessels, corticosteroids increased MMP-9 at week 2 and decreased MMP-1 at week 12 (P < 0.05). No effects were found in the glands.

Conclusions

Treatment of nasal polyposis with corticosteroids reduces both tissue eosinophilia and MMP expression in eosinophils while modifying the expression of remodeling markers in nasal polyp structural cells.

With the increasing use of individualized medical care (personalized medicine) in treating and managing patients with cancer, the utilization of biomarkers in selecting and tailoring such medical approaches also is increasing and becoming more important. Specifically, many therapies are effective against only a subgroup of a specific type of tumors and exposing patients with different non-responsive subgroups of the same tumor to ineffective therapies, not only exposes these patients needlessly to acute and chronic side effects of the therapy, but also adds to the costs of medical care. For example, the Oncotype Dx test for estrogen receptor positive tumors that are node negative has been used to identify low risk tumors for which surgery alone is an adequate therapy. Biomarkers may be used to aid in multiple aspects of medical care related to cancer, including early detection, diagnosis, risk assessment, as well as in predicting the aggressiveness of cancers (i.e., prognosis) and predicting the therapeutic efficacy of treatments (i.e., prediction). Biomarkers may be also used as surrogate endpoints to aid in evaluating therapies and preventive approaches. Types of biomarkers vary greatly and include histopathologic appearance, stage of the lesion, quantitative morphologic features, size of the lesion, metastatic pattern and extent of metastasis, as well as imaging and molecular features. The types of measurements of biomarkers also vary; for example, molecular features can be measured at the DNA, mRNA or protein levels as well as at regulatory levels (e.g., microRNA). The usefulness of each biomarker is limited by its sensitivity and specificity in fulfilling its role (e.g., in early detection) and the requirements of sensitivity and specificity to accomplish specific tasks are affected by multiple variables. For example, both very high specificity and sensitivity of a test are required to screen a population with a low prevalence of a specific tumor. The goal of this manuscript is to introduce the reader to how biomarkers may be used and the limitations on the uses of biomarkers in translational research.

Background

There is a growing evidence that rhinosinusitis may be associated with asthma as different manifestations of the same disorder. Several reports suggest the effectiveness of endoscopic sinus surgery (ESS) in asthmatic patients with chronic rhinosinusitis (CRS). Whether ESS has a positive effect on the clinical course of asthma still remains controversial. The aim of this study was to investigate the outcomes of ESS on asthma in patients with coexistent CRS.

Materials and methods

We performed a study to evaluate the effectiveness of ESS in 70 patients of CRS with associated asthma. The study compares changes in symptoms, medication and objective measures like pulmonary function in patients with persistent bronchial asthma and CRS before and after ESS.

Results

Following ESS, there was an improvement in the mean asthma symptoms (wheeze, cough and shortness of breath) and asthma medication use. The number of emergency department visits and hospital admissions also showed a reduction postsurgery. Objective analysis with pulmonary function tests revealed an improvement in the predicted scores. Three patients with extensive polyposis showed poor improvement after surgery and needed revision.

Conclusions

This study provides corroborative subjective and objective evidence that ESS is efficacious in the management of patients with CRS and asthma.

OBJECTIVE

Anti-platelet therapy with aspirin is the cornerstone of treatment after coronary artery bypass grafting (CABG). Aspirin resistance describes the clinical observation of the inability of aspirin to prevent thrombotic complications or the laboratory phenomenon of absence of the effect of aspirin on platelet inhibition tests. Off-pump CABG (OPCAB) is associated with reduced platelet activation and turnover compared to on-pump surgery which may indicate that aspirin is more effective after OPCAB. Our aim was to evaluate the efficacy of aspirin and incidence of aspirin resistance in patients undergoing OPCAB.

METHODS

A total of 331 patients was recruited, of which 111 underwent primary OPCAB (group A) and 220 controls with ischaemic heart disease received medical therapy. Arachidonic acid-induced platelet aggregation and urinary 11-dehydro thromboxane B2 (11-dehydroTxB2) were measured at baseline and following aspirin administration on days 1, 4 and 10. A 6-month follow-up was completed in patients who developed aspirin resistance.

RESULTS

On the first postoperative day, 78 patients (70.3%) were aspirin sensitive (AS) and 33 (29.7%) were aspirin resistant (AR). Of the latter, 18 (16.2%) and five (4.5%) patients remained resistant on days 4 and 10, respectively. AR patients had significantly greater platelet aggregation and urinary 11-dehydroTxB2 levels at all time points than those in the AS group. All patients in the AR group were AS by 6 months. All controls were sensitive to aspirin with similar platelet aggregation and 11-dehydroTxB2 to those in the AS group.

CONCLUSIONS

Aspirin resistance is a transient phenomenon during the early postoperative period in approximately 30% of patients undergoing OPCAB.