Nasal endoscopy in asthmatic children: assessment of rhinosinusitis and adenoiditis incidence, correlations with cytology and microbiology

BACKGROUND: Upper respiratory airway diseases may induce a worsening of asthma. Sinusitis represents one of the most common chronic diseases. The association of asthma and sinusitis varies greatly in different studies, depending on diagnostic procedures. OBJECTIVE: The aims were: (i) to demonstrate that nasal endoscopy may be easily feasible in asthma at paediatric age; (ii) to evaluate the incidence of rhinosinusitis and adenoiditis in children with asthma by nasal endoscopy; (iii) to correlate inflammatory parameters such as cytology and microbiological cultures with nasal endoscopy findings. SUBJECTS AND METHODS: One hundred and forty-five asthmatic children were evaluated, 48 males and 97 females, with an average age of 7.27 years. Evaluated parameters were the incidence of rhinosinusal infections in asthmatic children, and the role of: (i) nasal endoscopy, (ii) nasal cytology, and (iii) nasal microbiology in their diagnoses. RESULTS: Nasal endoscopy was successfully performed on 128 patients. Twenty-six children had endoscopic rhinosinusitis alone, 10 had adenoiditis alone, and 35 showed endoscopic rhinosinusitis associated with adenoiditis. There were significant correlations between endoscopic rhinosinusitis and adenoiditis (P < 0.001), between clinical and endoscopic rhinosinusitis (P < 0.001), between endoscopic rhinosinusitis and adenoiditis and microbiology (P < 0.05 and P < 0.0001, respectively), and between microbiology and cytology (P < 0.05). CONCLUSION: This study shows that rhinosinusal infections are common in asthmatic children. Moreover, nasal endoscopy might represent a fruitful tool in the management of asthmatic children.     

Cytokine pattern in allergic and non-allergic chronic rhinosinusitis in asthmatic children

BACKGROUND: Rhinosinusitis represents one of the most common chronic diseases. The association of rhinosinusitis with asthma has been frequently reported. Eosinophils and Th2 cells play a pathogenic mechanism in asthma. OBJECTIVE: The aims of the study were to evaluate the cytokine pattern in chronic rhinosinusitis in asthmatic children and to compare the findings in allergic vs. non-allergic asthmatics. METHODS: Thirty-five asthmatic children were evaluated, 19 males and 16 females, with an average age of 8.7 years. All children were asthmatic and suffered from chronic rhinosinusitis. Twenty were allergic and 15 were non-allergic. Ten healthy children were studied as normal controls. Evaluated parameters were the levels of the following cytokines: IL-1beta, IL-4, IL-6, IL-8, IL-12, IFN-gamma and TNF-alpha. Cytokines were recovered from rhinosinusal lavage and measured by immunoassays. Nasal cytology was also performed in all subjects and inflammatory cells were counted by conventional staining. RESULTS: Allergic subjects showed a significant increase of IL-4 (P < 0.01) and TNF-alpha (P < 0.05) and a significant decrease of IL-12 (P < 0.05) and of IFN-gamma (P < 0.0001), whereas IL-1beta, IL-6 and IL-8 were not significantly increased. Non-allergic children showed a significant increase of IL-4 (P < 0.05) and a significant decrease of IFN-gamma (P < 0.0001), IL-12 was not significantly decreased, and IL-1beta, IL-6 and IL-8 were not significantly increased. A significant inflammatory infiltrate was present in all asthmatic children. Significant correlations were demonstrated between IL-4 and IL-12 (P < 0.001), IL-12 and IFN-gamma (P < 0.001), IL-8 and neutrophils (P < 0.01), and TNF-alpha and monocytes/macrophages (P < 0.05), in allergic asthmatics. IL-4 and IL-12 were significantly correlated (P < 0.05) as well as IL-8 and neutrophils (P < 0.01) in non-allergic asthmatics. CONCLUSION: This study shows that allergic asthmatic children with chronic rhinosinusitis have a typical Th2 cytokine pattern, but also non-allergic asthmatic children share a similar pattern. These findings would suggest the existence of a common pathophysiological mechanism shared by upper and lower airways and are consistent with the concept of united airways disease.     

Early effects of aspirin desensitization treatment in asthmatic patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin (ASA)-exacerbated respiratory disease (AERD) is characterized by aggressive inflammation of the respiratory tract and often requires topical and/or systemic corticosteroids to maintain partial control of this disease. Previous studies have revealed that ASA desensitization and subsequent treatment with ASA is associated with clinical improvement in AERD. OBJECTIVE: The aim of the present study was to determine the effect of daily ASA treatment for the first 4 weeks after ASA desensitization. METHODS: Thirty-eight patients underwent ASA oral challenge followed by ASA desensitization and daily ASA therapy. Changes in nasal and asthma symptoms, combined with changes in oral prednisone, were recorded daily during 4 weeks before and after desensitization. Severity of symptoms ranged from a scale of 1 to 5 (1 = asymptomatic and 5 = most severe symptoms). For statistical analyses the sum of nasal symptoms and asthma symptoms was calculated. Olfactory scores were also analyzed. RESULTS: Nasal and asthma symptom scores, as well as olfactory scores, improved significantly (P < 0.0001). For the 15 patients taking prednisone, their mean doses decreased from 10.7 to 5.9 mg daily (P = 0.0003). CONCLUSIONS: Our study suggests that ASA desensitization treatment is effective during the first 4 weeks of daily treatment with ASA.     

Natural history and clinical features of aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis, nasal polyposis, asthma and precipitation of asthma, and rhinitis attacks after ingestion of aspirin (ASA) and most other nonsteroidal antiinflammatory drugs (NSAIDs). Although precipitation of asthma attacks by ingestion of ASA and other NSAIDs is considered a hallmark of the syndrome, the respiratory mucosal inflammatory disease process begins and continues in the absence of ongoing or even intermittent exposure to ASA or NSAIDs. The typical patient with AERD is an adult who develops refractory chronic rhinitis in the third or fourth decade of life. The chronic rhinitis evolves into chronic eosinophilic rhinosinusitis with associated nasal polyposis. Anosmia appears in most patients. CT of the sinuses most often demonstrates pansinusitis and patients often undergo multiple sinus operations resulting in only limited temporary benefit. During the evolution of the sinus disease persistent asthma develops. Finally, if patients are exposed to ASA or NSAIDs acute respiratory reactions begin to occur. Despite subsequent avoidance of ASA and other NSAIDs, the respiratory mucosal inflammatory disease persists, often requiring systemic corticosteroids for control of both upper- and lower-respiratory tract symptoms. Adequate control of asthma can often only be accomplished with the simultaneous control of the associated rhinosinusitis. With few exceptions, once AERD develops it remains for the remainder of the patient’s life. Formerly Scripps Clinic and Green Hospital, La Jolla, CA     

Oral versus intravenous corticosteroids in children hospitalized with asthma

BACKGROUND: Previous studies have demonstrated that in the emergency treatment of an asthma exacerbation, corticosteroids used in conjunction with beta-agonists result in lower hospitalization rates for children and adults. Furthermore, orally administered corticosteroids have been found to be effective in the treatment of outpatients with asthma. However, similar data in inpatients is lacking. OBJECTIVE: The purpose of this study was to determine the efficacy of oral prednisone versus intravenous methylprednisolone in equivalent doses for the treatment of an acute asthma exacerbation in hospitalized children. METHODS: We conducted a randomized, double-blind, double-placebo study comparing oral prednisone at 2 mg/kg/dose (maximum 120 mg/dose) twice daily versus intravenous methylprednisolone at 1 mg/kg/dose (maximum 60 mg/dose) four times daily in a group of patients 2 through 18 years of age hospitalized for an acute asthma exacerbation. All patients were assessed by a clinical asthma score 3 times a day. The main study outcome was length of hospitalization; total length of stay and time elapsed before beta-agonists could be administered at 6-hour intervals. Duration of supplemental oxygen administration and peak flow measurements were secondary outcome measures. RESULTS: Sixty-six patients were evaluated. Children in the prednisone group had a mean length of stay of 70 hours compared with 78 hours for the methylprednisolone group (P =.52). Children in the prednisone group were successfully weaned to beta-agonists in 6-hour intervals after 59 hours compared with 68 hours for the methylprednisolone group (P =.47). Patients receiving prednisone required supplemental oxygen for 30 hours compared with 52 hours for the methylprednisolone group (P =.04). CONCLUSION: There was no difference in length of hospital stay between asthmatic patients receiving oral prednisone and those receiving intravenous methylprednisolone. Because hospitalization charges are approximately 10 times greater for intravenous methylprednisolone compared with oral prednisone, the use of oral prednisone to treat inpatients with acute asthma would result in substantial savings.     

Management approaches to intermittent wheezing in young children

PURPOSE OF REVIEW: To review the recently published studies addressing various treatment approaches for episodic wheezing in young children. RECENT FINDINGS: A landmark study demonstrated that short courses of oral corticosteroids initiated at the first sign of an upper respiratory tract infection decreased wheezing episode frequency and severity. Since then, alternative treatment strategies have been investigated. Montelukast decreased short-term daytime cough and delayed exacerbations following hospitalization for respiratory syncytial virus bronchiolitis, and led to fewer exacerbations without decreasing oral corticosteroids use among children with intermittent asthma. Preschool children with frequent wheezing at high risk for asthma receiving daily inhaled corticosteroids experienced lower rates of exacerbations requiring oral corticosteroids. Episodic use of inhaled corticosteroids, initiated at the early signs of an upper respiratory infection, led to modest reduction in symptoms, but not oral corticosteroid use. Among young children with 'preasthma', inhaled corticosteroids initiated after 3 days of wheezing did not affect the frequency or severity of wheezing episodes. SUMMARY: Evidence for the preferred treatment strategies for intermittent wheezing in young children remains incomplete. Most of the studies represent heterogeneous populations and lack adequate statistical power to evaluate relevant outcomes. Based on the evidence, there is rationale for further investigation of several management strategies, including corticosteroids and/or leukotriene receptor antagonists administered daily or episodically.     

Steroids and antibiotics for treatment of acute asthma exacerbations in African-American children

BACKGROUND: There has been great debate surrounding the appropriate treatment regimens in children who present with acute asthma exacerbations secondary to upper respiratory tract infections. OBJECTIVE: To determine whether treatment with corticosteroids alone or in combination with antibiotics will decrease respiratory symptoms in children who develop asthma exacerbations secondary to upper respiratory tract infections. METHODS: A retrospective cohort control study involving 86 African-American children, ages 5-16, with mild intermittent asthma. The patients were treated with an albuterol inhaler (control group), inhaler plus five days of Prednisone; or inhaler, Prednisone, and 10 days of Amoxicillin. All patients were assessed regarding peak flows, albuterol inhaler usage, and symptomatology. RESULTS: On follow up five- to seven days after presentation, the corticosteroids group demonstrated a marked improvement in peak flows (88% versus 77%) and a significantly lower albuterol inhaler usage rate (2.2 versus 3.7 times a day) relative to the control group. The corticosteroids plus antibiotics group demonstrated peak flows (86% versus 88%) and inhaler usage (2.4 versus 2.2) nearly identical to corticosteroids alone, but the severity of underlying respiratory symptoms was significantly less. CONCLUSION: A five-day course of oral corticosteroids will significantly improve lung function and lessen severity of asthma symptoms. The addition of antibiotics to the treatment regimen has no additive effect on the reactive airway symptoms.     

Failure of tacrolimus to prevent aspirin-induced respiratory reactions in patients with aspirin-exacerbated respiratory disease

BACKGROUND: In patients with aspirin-exacerbated respiratory disease (AERD), pretreatment with asthma controller medications (leukotriene modifiers, inhaled or systemic corticosteroids, and salmeterol) partially modifies the severity of aspirin-induced asthmatic reactions. OBJECTIVE: A recent study showed that pretreatment with tacrolimus completely prevented aspirin-induced respiratory reactions and might allow silent aspirin desensitization. METHODS: Ten patients with rhinosinusitis, nasal polyps, and asthma had a history of asthma attacks after ingesting aspirin and nonsteroidal anti-inflammatory drugs. All underwent baseline oral aspirin challenges and had typical respiratory reactions. They were then randomized to receive tacrolimus (0.1 mg/kg weight; 8 patients) or placebo (2 patients) in a double-blind protocol before rechallenge with aspirin using the previous provoking dose of aspirin. In addition, respiratory reactions sustained by 50 consecutive patients with AERD during 2004 were recorded, analyzed, and compared with the tacrolimus/placebo-treated patients to determine whether there were any differences. RESULTS: Tacrolimus pretreatment failed to block respiratory reactions to provoking doses of aspirin in 5 of 8 patients with AERD, and in the other 3 patients did not block higher doses of aspirin. The results of oral aspirin challenges in the control population of 50 patients were compared with either the baseline or postchallenge data from the tacrolimus-pretreated or placebo-pretreated patients with AERD, and there were no significant differences. CONCLUSIONS: Use of tacrolimus as add-on pretreatment to prevent reactions to aspirin in patients with AERD or to achieve the goal of silent aspirin desensitization could not be accomplished.     

Continuous antihistamine treatment controls allergic inflammation and reduces respiratory morbidity in children with mite allergy

BACKGROUND: Allergic reaction is characterized by a complex inflammatory process. Some of the new antihistamines have antiallergic effects and can affect the inflammatory cell recruitment via adhesion molecule downregulation. We aimed to assess in a 12-month study whether continuous treatment with an antihistamine (terfenadine) can reduce respiratory symptoms and local inflammation in children with mite allergy. METHODS: The study was double-blind and placebo-controlled: it involved two parallel groups of children suffering from rhinoconjunctivitis and/or mild intermittent asthma due to mite allergy. They received either terfenadine (1 mg/kg per body weight per day) or placebo for 1 year. Nasal, conjunctival, and bronchial symptoms were recorded by diary cards; at each of the programmed control visits, a nasal scraping for inflammatory cells and ICAM-1 was performed. Some additional clinical parameters were also recorded: days of school absence, extra visits for acute respiratory symptoms, and days of hospital admission. RESULTS: Only children treated with terfenadine achieved significant control of symptoms (P<0.05 in 8 out of 12 months) and allergic inflammation, as shown by inflammatory cell infiltrate and ICAM-1 expression at nasal level (P<0.001), and had significantly fewer extra visits and school absences than the placebo group (P<0.03). No side-effects were reported in either group. CONCLUSIONS: The present study demonstrates that continuous terfenadine treatment (1 mg/kg body weight per day) could decrease respiratory symptoms and allergic inflammation, and it had an additional antiallergic effect in reducing ICAM-1 expression on nasal epithelial cells. Therefore, the present results confirm the efficacy of a long-term therapeutic strategy in controlling allergic inflammation.     

Acute effects of Asian dust events on respiratory symptoms and peak expiratory flow in children with mild asthma

The aim of this study was to investigate the possible adverse effects of Asian dust events on respiratory health in asthmatic children. Fifty-two children with mild asthma were studied for eight consecutive weeks in the spring of 2004 (March 8 to May 2). During the study period, five Asian dust days were identified; we included a lag period of two days following each of the events. Subjects recorded their respiratory symptom diaries and peak expiratory flow (PEF) twice daily during the study period; and they underwent methacholine bronchial challenge tests. The subjects reported a significantly higher frequency of respiratory symptoms during the Asian dust days than during the control days. They showed significantly more reduced morning and evening PEF values, and more increased PEF variability (10.1%+/-3.5% vs. 5.5%+/-2.2%) during the Asian dust days than during the control days. Methacholine PC(20) was not significantly different between before and after the study period (geometric mean: 2.82 mg/mL vs. 3.16 mg/mL). These results suggest that the short-term Asian dust events might be associated with increased acute respiratory symptoms and changes in PEF outcomes. However, there might be little long-term influence on airway hyperresponsiveness in children with mild asthma.     

Treating acute rhinosinusitis: comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo

BACKGROUND: Intranasal corticosteroids used with antibiotics are known to improve rhinosinusitis symptoms compared with antibiotic therapy alone. However, the efficacy of intranasal corticosteroid monotherapy for acute, uncomplicated rhinosinusitis is not established. OBJECTIVES: To evaluate efficacy and safety of mometasone furoate nasal spray (MFNS) versus amoxicillin and placebo in patients with acute, uncomplicated rhinosinusitis. METHODS: In this double-blind, double-dummy trial, subjects (> or =12 years; N = 981) were randomized to MFNS 200 microg once daily or twice daily for 15 days, amoxicillin 500 mg 3 times daily for 10 days, or respective placebo. Follow-up was 14 days. The primary efficacy endpoint was mean am/pm major symptom score over the treatment phase. Secondary efficacy endpoints included total symptom score. Safety assessments included disease recurrence during follow-up and adverse event monitoring. RESULTS: Mometasone furoate nasal spray 200 microg twice daily was significantly superior to placebo (P < .001) and amoxicillin (P = .002) at improving major symptom score. Starting on day 2, MFNS 200 microg twice daily improved total symptom score throughout treatment versus amoxicillin (P = .012) and placebo (P < .001). Global response to treatment was significantly greater with MFNS 200 microg twice daily versus amoxicillin (P = .013) and placebo (P = .001). Although significantly superior to placebo, MFNS 200 microg once daily was not superior to amoxicillin for the primary or secondary efficacy endpoints. All treatments were well tolerated with a similar incidence of adverse events. CONCLUSION: In patients with acute, uncomplicated rhinosinusitis, MFNS 200 microg twice daily produced significant symptom improvements versus amoxicillin and placebo, without predisposing the patient to disease recurrence or bacterial infection.     

Rhinosinusitis in severe asthma

BACKGROUND: Chronic rhinosinusitis is a common comorbidity of asthma. However, sinonasal involvement in severe steroid-dependent asthma is still undefined. OBJECTIVE: The aim of the study was to evaluate chronic rhinosinusitis in 35 patients with severe steroid-dependent asthma by using a clinical score and coronal computed tomography (CT) scanning. METHODS: Thirty-five subjects (16 female subjects) with severe asthma requiring daily doses of oral corticosteroids were compared with 34 patients (19 female patients) with mild-to-moderate asthma. Sinonasal involvement was studied by using clinical and CT scores. Airflow obstruction, therapy requirement, and asthma triggering factors were carefully assessed. RESULTS: The proportion of patients with symptoms of rhinosinusitis was similar in both groups of asthmatic subjects (74% in patients with severe steroid-dependent asthma and 70% in patients with mild-to-moderate asthma). All subjects with steroid-dependent asthma versus 88% of subjects with mild-to-moderate asthma had abnormal CT scan results. The clinical (P <.05) and CT scan (P <.0005) severity scores were higher in the subjects with severe steroid-dependent asthma. In both groups the CT scan scores were correlated to the clinical scores (P <.0001 and P <.006), but only in the mild-to-moderate group were both scores correlated with high significance (P <.002 and P <.0005) to the absolute number of blood eosinophils. CONCLUSION: Frequency of rhinosinusitis in patients with mild-to-moderate or severe steroid-dependent asthma is similar; however, sinonasal involvement, as evaluated by clinical symptoms and CT scan imaging, is significantly greater in the patients with severe steroid-dependent asthma than in those with mild-to-moderate asthma.     

Fluticasone propionate aqueous nasal spray does not influence the recurrence rate of chronic rhinosinusitis and nasal polyps 1 year after functional endoscopic sinus surgery

BACKGROUND: Local corticosteroids are widely used in the treatment of nasal polyps and chronic rhinosinusitis both before and after nasal surgery. Their efficacy after functional endoscopic sinus surgery (FESS) has not been fully established by placebo-controlled trials. OBJECTIVE: This double-blind placebo-controlled randomized study was performed in order to investigate whether fluticasone propionate aqueous nasal spray (FPANS) reduces the recurrence rate of nasal polyps and chronic rhinosinusitis during the first year after FESS. PATIENTS AND METHODS: The trial looked at 162 patients aged 18 years and older requiring FESS for chronic rhinosinusitis or nasal polyps. After FESS combined with peri-operative systemic corticosteroids, patients were randomized and given FPANS 400 microg b.i.d., FPANS 800 microg b.i.d. or placebo b.i.d. for the duration of 1 year. Patients were withdrawn from the trial (but still included in the study for statistical purposes) if there were recurrent or persistent diseases, defined as progressive regrowth of nasal polyps, recurrent signs and symptoms of chronic sinusitis combined with abnormalities on computed tomography scan and persistent complaints for at least 2 months after FESS. RESULTS: A significant reduction of symptoms was seen after FESS. After 1 year, 46 patients had been withdrawn from the trial because of recurrent diseases and 32 patients because of persistent symptoms. No differences in the number of patients withdrawn because of recurrent or persistent diseases were found between the patients treated with FPANS and patients treated with placebo. We were also unable to find a positive effect of FPANS compared with placebo in several subgroups such as patients with nasal polyps, high score at FESS or no previous sinus surgery. CONCLUSION: This placebo-controlled study does not show that treatment with FPANS up to 1 year after FESS had a positive effect compared with placebo.     

How should nasal symptoms be investigated in asthma? A comparison of radiologic and endoscopic findings

BACKGROUND: To improve asthma control, the management of rhinosinusitis often leads the physician to perform sinonasal imaging and/or nasal endoscopy, but their respective contributions are still insufficiently understood. OBJECTIVE: To evaluate the potential contribution of a symptoms questionnaire, sinus radiography (SR) and computed tomography (CT) scan to the diagnosis of nasal diseases in asthmatic patients when compared with ENT examination. METHODS: A total of 124 patients completed a questionnaire on nasal symptoms administered by the chest physician. Then, they underwent ENT examination. On the same day, SR and CT scans were performed independently. RESULTS: Patients (80.3%) had nasal symptoms during the month preceding the consultation. The ENT examination was normal in 8.1% (n = 10) and revealed rhinitis in 57.3% (n = 71), rhinosinusitis in 14.5% (n = 18) and nasal polyposis in 20.2% (n = 25). For rhinitis, the negative predictive value of bilateral nasal obstruction was 87.8%. Both SR and CT had low sensitivity and specificity. For rhinosinusitis, the negative predictive value of nasal symptoms varied from 85.4 to 95.2%. Sinus CT was at least as accurate as SR for the diagnosis of rhinosinusitis. In a multivariate analysis, only the CT scan (score > or =12) appeared to be significantly associated with the diagnosis of nasal polyposis. CONCLUSION: In asthmatic patients, physicians need to enquire systematically about the existence of nasal symptoms by using this simple questionnaire which is sensitive for rhinitis, and has good negative predictive value for excluding rhinosinusitis and nasal polyposis.     

Role of staphylococcal superantigens in upper airway disease

PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps often represents a chronic severe inflammatory disease of the upper airways and may serve as a model for lower airway diseases such as late-onset intrinsic asthma. Enterotoxins derived from Staphylococcus aureus have been implicated in the pathophysiology of nasal polyps as disease-modifying factors; recent findings using therapeutic proof-of-concept approaches support this hypothesis. RECENT FINDINGS: Nasal polyps (chronic rhinosinusitis with nasal polyps) are characterized by a T-helper-2 dominated cytokine pattern that includes interleukin-5 and formation of immunoglobulin E. This is in contrast to chronic rhinosinusitis without polyps, which exhibits T-helper-1 biased cytokine release. It is now evident that the cytokine environment is decisive regarding the impact of S. aureus derived enterotoxins, which function as superantigens. S. aureus enterotoxin B further shifts the cytokine pattern in nasal polyps toward T-helper-2 cytokines (increases greater than twofold for interleukin-2, interleukin-4 and interleukin-5), but it disfavours the T-regulatory cytokines interleukin-10 and transforming growth factor-beta1. Furthermore, S. aureus derived enterotoxins influence local immunoglobulin synthesis and induce polyclonal immunoglobulin E production, which may contribute to severe inflammation via activation of mast cells. SUMMARY: From this new understanding of chronic rhinosinusitis with nasal polyps, new therapeutic approaches emerge such as anti-interleukin-5, anti-immunoglobulin E, and antibiotic treatment. These may enlarge the nonsurgical armentarium.     

Aspirin-sensitive rhinosinusitis asthma: a double-blind crossover study of treatment with aspirin

Twenty-five ASA-sensitive patients with rhinosinusitis asthma underwent oral ASA challenges followed by desensitization to the adverse respiratory effects of ASA. We then compared the efficacy of continuous ASA treatment for their respiratory tract disease to that of a placebo treatment during a double-blind crossover study. For this group of 25 patients, there was significant improvement in nasal symptoms and a reduction in use of nasal beclomethasone during the months when they received ASA treatment. Lower respiratory tract symptoms, values of FEV1, and the use of antiasthmatic medications including prednisone were not significantly changed during ASA treatment. Desensitization to ASA followed by ASA treatment appears to significantly alleviate symptoms of rhinosinusitis. However, only half the patients experienced improvement in their asthma symptoms during ASA treatment.     

Lack of relationship between eosinophil cationic protein and eosinophil protein X in nasal lavage and urine and the severity of childhood asthma in a 6-month follow-up study.

BACKGROUND: Recent studies suggest that eosinophil cationic protein (ECP) and eosinophil protein X (EPX) may be valuable markers of airway inflammation in various body fluids of asthmatic children. Most of these studies have relied on a single measure of inflammatory markers. OBJECTIVE: We measured ECP and EPX in nasal lavage fluids (NALF) and urine samples in children with asthma over a 6-month period to study the relationship between inflammatory markers and clinical severity. METHODS: Fourteen children with mild persisting asthma (mean age 11.7 years, SD 2.2) were recruited. All patients were on therapy including inhaled steroids. For a 6-month period asthma severity was monitored by at least monthly physical examination and pulmonary function tests. Daily morning and evening PEF, asthma symptoms and medication were recorded in diaries for the whole study period. Telephone interviews were performed between visits and additional visits were done in case of an increase in asthmatic symptoms or drop of PEF values under 80% of best value. An exacerbation was defined by a fall of FEV1 > 10% and an increase in asthma symptoms and additional need of beta2-agonist. NALF and urine samples were obtained at each visit and analysed for ECP (NALF only) and EPX. RESULTS: Mean observation time was 186.4 days (SD 19.8). Thirteen patients completed the study. During the study period 11 exacerbations were observed in six patients. No significant associations between PEF, PEF variability (amplitude % of mean), daily symptoms, additional beta2-agonist, FEV1 and MEF50 and nasal ECP, nasal EPX and urinary EPX were found. However, at exacerbations an average increase of nasal ECP (9.3 vs 50.3 microg/L) and EPX (nasal EPX 36.4 vs 141.7 microg/L, urinary EPX 46.4 vs 74.1 microg/mmol creatinine) was observed. CONCLUSION: Serial measurements of ECP and EPX in NALF and urine samples do not provide additional information for the practical management in monitoring childhood asthma.     

Aspirin-induced asthma: advances in pathogenesis,diagnosis, and management

In some asthmatic individuals, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygen-ase 1 (COX-1) exacerbate the condition. This distinct clinical syndrome, called aspirin-induced asthma (AIA), is characterized by an eosinophilic rhinosinusitis, nasal polyposis, aspirin sensitivity, and asthma. There is no in vitro test for the disorder, and diagnosis can be established only by provocation challenges with aspirin or NSAIDs. Recent major advances in the molecular biology of eicosanoids, exemplified by the cloning of 2 cysteinyl leukotriene receptors and the discovery of a whole family of cyclooxygenase enzymes, offer new insights into mechanisms operating in AIA. The disease runs a protracted course even if COX-1 inhibitors are avoided, and the course is often severe, many patients requiring systemic corticosteroids to control their sinusitis and asthma. Aspirin and NSAIDs should be avoided, but highly specific COX-2 inhibitors, known as coxibs, are well tolerated and can be safely used. Aspirin desensitization, followed by daily aspirin treatment, is a valuable therapeutic option in most patients with AIA, particularly those with recurrent nasal polyposis or overdependence on systemic corticosteroids.     

Effective dose range of mometasone furoate nasal spray in the treatment of acute rhinosinusitis.

BACKGROUND: Mometasone furoate nasal spray (MFNS) 400 microg, twice daily, as adjunctive treatment with oral antibiotic significantly improved symptoms of recurrent rhinosinusitis. OBJECTIVE: To evaluate the effectiveness and safety of MFNS 200 microg, twice daily, and 400 microg, twice daily, compared with placebo as adjunctive treatment with oral antibiotic for acute rhinosinusitis. METHODS: In this multicenter, double-blind, placebo-controlled study, 967 outpatients with computed tomographic scan-confirmed moderate to severe rhinosinusitis received amoxicillin/clavulanate potassium (Augmentin, GlaxoSmithKline, Research Triangle Park, NC) 875 mg, twice daily, for 21 days with adjunctive twice daily MFNS 200 microg, MFNS 400 microg, or placebo nasal spray. Patients recorded scores of six rhinosinusitis symptoms and any adverse events twice daily. Pre- and postcosyntropin-stimulation plasma cortisol levels were measured in a subset of patients at selected study sites. RESULTS: Treatment with MFNS 200 microg or 400 microg, twice daily, produced significantly greater improvements in total symptoms score (primary efficacy variable) day 1 to day 15 average (50% and 51%, respectively) than placebo (44%, P < or = 0.017). Both doses of MFNS produced significant total symptoms score improvement over placebo by day 4, and maintained efficacy over the entire 21-day study. Relief of individual symptoms showed a similar pattern. Both doses of MFNS were well tolerated, and adverse events were similar to that of placebo. Cosyntropin stimulation showed no evidence of hypothalamic-pituitary-adrenal axis suppression. CONCLUSIONS: As adjunctive therapy to oral antibiotic treatment, MFNS at doses of 200 microg or 400 microg, twice daily, was well tolerated and significantly more effective in reducing the symptoms of rhinosinusitis than antibiotic therapy alone.