Diagnostic value of clinical parameters in the prediction of aspirin-exacerbated respiratory disease in asthma

Purpose

Aspirin-exacerbated respiratory disease (AERD) has attracted a great deal of attention because of its association with increased asthma severity. However, oral aspirin challenge (OAC) to diagnose AERD is a time-consuming procedure, and some patients experience serious complications. Thus, we evaluated diagnostic values of non-invasive clinical parameters to predict AERD in asthmatic patients.

Methods

A total of 836 Korean subjects were recruited from an asthma cohort. They underwent OAC, and clinical parameters including the history of aspirin hypersensitivity, nasal polyposis, and chronic sinusitis of aspirin-tolerant asthma (ATA) and AERD asthmatic patients were compared.

Results

Significant differences (P<0.01) were found in eight parameters: age at diagnosis, body mass index, FEV1%, PC20, history of urticaria, nasal polyps, chronic sinusitis, and history of aspirin hypersensitivity. After logistic regression analysis based on the eight clinical parameters, nasal polyps, history of aspirin intolerance, sinusitis, and log [PC20 methacholine] remained significantly associated with AERD (P<0.05). The sensitivity and specificity of the history of aspirin hypersensitivity to predict AERD were 64.7% and 92.0%, respectively, and the positive and negative predictive values were 56.9% and 94.1%, respectively. Overall, the accuracy of the test was 88.2%. The accuracy of the tests for nasal polyps and chronic sinusitis were 67.3% and 60.4%, respectively.

Conclusions

Among clinical parameters associated with AERD, the history of aspirin hypersensitivity has the best positive and negative predictive values for the oral aspirin challenge test. Because the false-positive and -negative rates were still high, additional non-invasive methods are needed to reduce the rate of false outcomes.     

Aspirin sensitivity and severity of asthma: evidence for irreversible airway obstruction in patients with severe or difficult-to-treat asthma

BACKGROUND: Patients with aspirin sensitivity experience hyperplastic sinusitis and nasal polyposis. We speculated that similar mechanisms could be acting in the lower airway and that these individuals would demonstrate more severe asthma and irreversible loss of lung function. OBJECTIVE: We sought to investigate the role of aspirin-exacerbated respiratory disease (AERD) as a risk factor for the development of irreversible airway obstruction. METHODS: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study is a multicenter observational study of subjects with severe or difficult-to-treat asthma. Data were compared between subjects who reported asthma exacerbation after aspirin ingestion and those who did not. The primary measure of bronchodilator-resistant obstruction (possible remodeling) was the maximally achieved postbronchodilator spirometry averaged over the 3-year duration of the study. RESULTS: Adult subjects (>/=18 years) with AERD (n = 459) were compared with subjects with non-aspirin-sensitive asthma (n = 2848). Subjects with AERD had significantly lower mean postbronchodilator percent predicted FEV(1) compared with subjects with non-aspirin-sensitive asthma (75.3% vs 79.9%, P < .001). Differences in spirometry between the 2 cohorts persisted after controlling for potential confounding variables. In addition, subjects with AERD were more likely to have severe asthma by means of physician assessment (66% vs 49%, P < .001), to have been intubated (20% vs 11%, P < .001), to have a steroid burst in the previous 3 months (56% vs 46%, P < .001), and to have required high-dose inhaled corticosteroids (34% vs 26%, P < .001). CONCLUSIONS: These data suggest that aspirin sensitivity is associated with increased asthma severity and possible remodeling of both the upper and lower airways.     

The natural history and clinical characteristics of aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinitis, nasal polyps, asthma, and precipitation of asthma and rhinitis attacks after ingestion of aspirin (ASA) and most nonsteroidal anti-inflammatory drugs (NSAIDs). Most information about the disease in the United States has come from small samples of patients. OBJECTIVE: The purpose of this study was to examine the natural history and clinical characteristics of 300 AERD patients, referred to our institution for aspirin desensitization. METHODS: All potential AERD patients were evaluated using a standard questionnaire that included information about clinical characteristics and natural progression of their disease, previous history of reactions to ASA and other NSAIDs, current use of medications, and ethnic backgrounds. All patients underwent oral ASA challenges to prove they had AERD. RESULTS: From patients' history we found that the average age at onset of AERD was 34 years, and that 57% were female. Counting ASA as an NSAID, 33% had previously reacted on two occasions to NSAIDs and 36% on more than three occasions to NSAIDs, whereas only 27% had reacted to one NSAID before they came to us for evaluation. Our patients had averaged 5.5 episodes of sinusitis per year. There were no significant differences in the clinical characteristics or use of medications between genders. Ethnicity was heterogeneous in most participants. CONCLUSIONS: AERD begins in the third decade of life and in both sexes. The disease progressed over the 13 years between historical onset and current evaluation, with more sinusitis and need for controller medications over time. There was no ethnic or familial distribution of AERD.     

Lipoxin A4 levels in asthma: relation with disease severity and aspirin sensitivity

BACKGROUND: Lipoxin (LX) A4, an endogenous anti-inflammatory eicosanoid, has been found to be low in patients with severe asthma. However, few studies also suggested more diminished LX A4 levels in aspirin-exacerbated respiratory disease (AERD) when compared with aspirin-tolerant asthma (ATA). It is, therefore, currently not clear whether the asthma severity or the presence of AERD has a primary role in the disturbed LX metabolism. OBJECTIVE: To detect LX A4 and 15-epi-LX A4 levels in asthma patients with and without AERD of comparable severity. METHODS: The study groups consisted of 22 subjects with AERD, 22 subjects with ATA and 10 volunteers without asthma and aspirin sensitivity. Whole-blood samples were stimulated with calcium ionophore, A23187 (5 x 10(-5) m) and A23187 (5 x 10(-5) m)+aspirin (10(-4) m). LX A4 and 15-epi-LX A4 levels were analysed by the enzyme immune assay method. RESULTS: Severe asthma patients in both AERD [0.5 (0.8)] ng/mL and ATA [0.5 (0.45) ng/mL] groups showed diminished generation for LX A4 to stimulation with A23187 in comparison with other severity degrees in their groups (P=0.02 and 0.046, respectively). LX A4 generation in both severe groups was comparable with each other (P>0.05). Although severe cases with AERD showed a diminished capacity to generate 15-epi-LX A4, this did not reach statistical significance. CONCLUSION: This study indicated that diminished LX A4 generation was unique to severe asthma phenotype regardless of comorbid aspirin sensitivity. Clinical Implications Lower LX A4 levels in severe asthma would suggest a possibility for LX analogues as future treatment options in these patients.     

Combined mediator blockade or topical steroid for treating the unified allergic airway

BACKGROUND: Asthma and allergic rhinitis are manifestations of a single unified allergic airway, for which the best treatment is uncertain. OBJECTIVE: To compare the anti-inflammatory efficacy in the unified allergic airway of combined oral mediator antagonism and combined topical steroid. METHODS: Subjects with asthma and perennial allergic rhinitis entered a randomized double blind crossover study comparing montelukast 10 mg and cetirizine 10 mg to extra-fine inhaled beclomethasone 400 mcg/day and intranasal beclomethasone 200 mcg/day, each taken once daily for 2 months, after 2-week placebo washouts. Measurements were made after each washout and randomized treatment, comprising: methacholine PC20, exhaled and nasal nitric oxide, blood eosinophils and eosinophilic cationic protein, symptoms, lung and nasal function tests. RESULTS: Seventeen patients completed per protocol. For PC20 and exhaled nitric oxide, only combined topical steroid produced improvements (P < 0.005) from placebo baseline. Combined steroid was superior by a 0.93 (95% CI 0.14-0.93, P < 0.05) doubling dilution difference for PC20 and a 0.99 (95% CI 0.9-15.1, P < 0.01) doubling difference for exhaled nitric oxide. Both treatments attenuated eosinophils and eosinophilic cationic protein, and reduced nasal symptoms (P < 0.05). Only steroid improved nasal nitric oxide (P=0.05) and asthma symptoms (P < 0.05). Neither treatment affected lung or nasal function tests. CONCLUSION: Combined topical steroid and combined mediator antagonism both attenuated systemic inflammation in the unified allergic airway, but only the former reduced bronchial and nasal inflammatory markers. The relevance of this to exacerbations and airway remodelling needs to be defined.     

Specific immunoglobulin E for staphylococcal enterotoxins in nasal polyps from patients with aspirin-intolerant asthma

BACKGROUND: Nasal polyps infiltrated with eosinophils are commonly found in chronic asthmatic patients, more frequently in those with aspirin-intolerant asthma (AIA) than aspirin-tolerant asthma (ATA). Some studies have suggested a contribution of superantigens derived from Staphylococcus sp to nasal polyposis and eosinophilia, but their relative importance in AIA and ATA subjects is unknown. OBJECTIVE: We investigated whether local production of specific IgE to staphylococcal enterotoxins A and B (SEA and SEB) and relationships with markers of eosinophilic inflammation differ in the nasal polyps of AIA and ATA subjects. METHODS: Fifteen AIA subjects with positive responses to lysine-aspirin bronchoprovocation and 15 ATA subjects underwent polypectomy. Immunoassays were used to quantify eosinophil cationic protein (ECP), IL-5, mast cell tryptase, soluble IL-2 receptors (sIL-2R), total IgE, and specific IgE for SEA and SEB. RESULTS: ECP levels in nasal polyp homogenates were higher in AIA subjects than in ATA subjects (P < 0.02), with no significant differences in tryptase, IL-5 or sIL-2R. Total IgE, and specific IgE to both SEA and SEB, were detectable in some nasal polyps from both subject groups, but median levels were markedly higher in AIA subjects than in ATA subjects (P = 0.04, 0.01, 0.05, respectively). Levels of specific IgE to SEA and SEB correlated significantly with levels of ECP and IL-5, but not those of tryptase or sIL-2R. CONCLUSION: These findings suggest that staphylococcal superantigens may drive local eosinophilic inflammation in nasal polyp tissue, and that this is exacerbated in subjects with AIA.     

Gene-expression profiles in human nasal polyp tissues and identification of genetic susceptibility in aspirin-intolerant asthma

Background Aspirin‐intolerant asthma (AIA) is a subtype of asthma induced by non‐steroidal anti‐inflammatory drugs and characterized by an aggressive mucosal inflammation of the lower airway (asthma) and the upper airways (rhinitis and nasal polyp). The lower airway lesion and the nasal polyp in AIA are postulated to have common pathogenic features involving aspirin sensitivity that would be reflected in the gene expression profile of AIA polyps. Objective This study was conducted to clarify the pathogenesis of AIA using gene expression analysis in nasal polyps, and identify genetic susceptibilities underlying AIA in a case–control association study. Methods Global gene expression of nasal polyps from nine AIA patients was examined using microarray technology in comparison with nasal polyps from five eosinophilic sinusitis (ES) patients, a related disease lacking aspirin sensitivity. Based on the AIA‐specific gene expression profile of nasal polyp, candidate genes for AIA susceptibility were selected and screened by a case–control design of 219 AIA patients, 374 non‐asthmatic control (CTR), and 282 aspirin‐tolerant asthmatic (ATA) subjects. Results One hundred and forty‐three elevated and three decreased genes were identified as AIA‐specific genes that were enriched in immune response according to Gene Ontology analysis. In addition, a k‐means‐based algorithm was applied to cluster the genes, and a subclass characteristic of AIA comprising 18 genes that were also enriched in immune response was identified. By examining the allelic associations of single nucleotide polymorphisms (SNPs) of AIA candidate genes relevant to an immune response with AIA, two SNPs, one each of INDO and IL1R2, showed significant associations with AIA (P=0.011 and 0.026 after Bonferroni's correction, respectively, in AIA vs. CTR). In AIA–ATA association analysis, modest associations of the two SNPs with AIA were observed. Conclusion These results indicate that INDO and IL1R2, which were identified from gene expression analyses of nasal polyps in AIA, represent susceptibility genes for AIA.     

Safety of high-dose rofecoxib in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by progressive sinusitis, nasal polyposis, and asthma that begins and continues in the absence of exposure to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Cross-sensitivity to all NSAIDs that inhibit cyclooxygenase-1 (COX-1) occurs in these individuals. Reactions to aspirin and NSAIDs in patients with AERD are largely due to inhibition of COX-1. Despite accumulating data on the safety of COX-2 selective inhibitors in AERD, concern still remains that high doses of a COX-2 inhibitor may be sufficient to induce a cross-reaction. OBJECTIVE: To determine whether high-dose rofecoxib cross-reacts in patients with AERD and asthma. METHODS: Sixty asthmatic patients underwent blinded placebo-controlled oral challenges with 50 mg of rofecoxib. Aspirin sensitivity was subsequently confirmed in all patients with the use of single-blinded aspirin challenges. RESULTS: None of the 60 patients experienced any symptoms, changes in nasal examination results, or declines in lung function during rofecoxib challenge. All 60 patients experienced respiratory reactions to aspirin challenge, with a mean provoking dose of 57 mg. The exact 1-sided 95% confidence interval for the underlying probability of 50 mg of rofecoxib inducing respiratory cross-reactions in patients with AERD is 0 to 0.05, or 0% to 5%. CONCLUSIONS: These results confirm the lack of cross-reactivity of aspirin and the highly selective COX-2 inhibitors in AERD. We suggest that it is time for the labeling of highly selective COX-2 inhibitors to reflect these data and for the warning that patients with AERD in particular and asthmatic patients in general avoid selective COX-2 inhibitors to be removed.     

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.     

Relationship among pulmonary function, bronchial reactivity, and exhaled nitric oxide in a large group of asthmatic patients.

BACKGROUND: Bronchial reactivity and exhaled nitric oxide (eNO) are not often used to monitor control and severity of asthma in clinical practice. OBJECTIVE: To evaluate the relationship among different physiologic measures (pulmonary function, nonspecific bronchial reactivity, and eNO) in asthmatic patients. METHODS: Cross-sectional, hospital-based study conducted in patients with varied asthma severity. RESULTS: A total of 392 patients participated in the study. There was no difference in eNO levels between patients taking inhaled corticosteroids (ICS group) and patients not receiving inhaled corticosteroids (NICS group). However, the percentage of predicted forced expiratory volume in 1 second (FEV1) and the provocative dose of methacholine causing a 20% decrease in FEV1 were significantly lower in the ICS group compared with the NICS group (mean, 83.2%; 95% confidence interval [CI], 80.4%-86.0%; vs mean, 94.1%; 95% CI, 91.1%-97.1%; P = .001; and geometric mean, 0.32 mg; 95% CI, 0.23-0.45 mg; vs geometric mean, 0.58 mg; 95% CI, 0.42-0.81 mg; P = .01; respectively). Patients with more severe bronchial hyperresponsiveness had a lower percentage of predicted FEV1 values (P < .001) and levels of eNO were significantly increased with increasing bronchial hyperresponsiveness (P < .001). There was no relationship between the percentage of predicted FEV1 and eNO. Atopic patients had significantly higher eNO levels than nonatopic patients (geometric mean, 11.21 ppb; 95% CI, 10.07-12.49 ppb; vs geometric mean, 7.76 ppb; 95% CI, 6.11-9.85 ppb; P = .006; respectively). CONCLUSIONS: eNO values are not related to the degree of airway obstruction but are related to airway reactivity and atopic status independent of inhaled corticosteroid use. Higher values of eNO are seen with increased airway reactivity.     

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     

PGE suppresses excessive anti-IgE induced cysteinyl leucotrienes production in mast cells of patients with aspirin exacerbated respiratory disease

BACKGROUND: Aspirin causes bronchospasm in patients with aspirin exacerbated respiratory disease (AERD). The contribution of mast cells to the increased cysteinyl-leucotrienes (cys-LTs) detected in AERD patients is however not defined. AIMS OF THE STUDY: Effects of prostaglandin (PG) E(2) and inhibitors of cyclooxygenase (COX) and lipoxygenase (LO) pathways on mediator release from cultured mast cells of normal subjects, aspirin tolerant asthma (ATA) and AERD patients were compared to better define the role of mast cells in AERD. METHODS: Mast cells were cultured from peripheral blood progenitors and were activated by anti-IgE. Histamine, PGD(2) and cys-LTs released were then determined. RESULTS: Basal release of all three mediators was similar in all subjects. Although the release of all three mediators was increased by anti-IgE, mast cells from AERD patients produced significantly more cys-LTs (6.9 +/- 2.0 ng/10(6) cells) than normal and ATA subjects (2.3 +/- 0.8 and 1.7 +/- 0.5 ng/10(6) cells, respectively). While COX and LO pathway inhibitors did not affect anti-IgE induced histamine release, they significantly suppressed the production of PGD(2) and cys-LTs, respectively, in all patients. PGE(2) significantly enhanced anti-IgE induced histamine and PGD(2) release from mast cells of normal subjects but not those of ATA and AERD patients. In contrast, PGE(2) suppressed only anti-IgE induced cys-LTs release from mast cells of AERD patients. CONCLUSION: We speculate that overproduction of cys-LTs is unique to mast cells of AERD patients and is particularly sensitive to suppression by PGE(2). Consequently reduction of PGE(2) production by aspirin removes this endogenous control of cys-LTs overproduction, resulting in asthma attack.     

Simvastatin does not exhibit therapeutic anti-inflammatory effects in asthma

BACKGROUND: Statins lower cholesterol and also exhibit anti-inflammatory properties. In vitro and animal studies have suggested they may be useful for the treatment of a number of inflammatory conditions. OBJECTIVE: To evaluate the in vivo therapeutic potential of simvastatin as an anti-inflammatory agent in patients with asthma. METHODS: Potential signal from treatment effect was optimized by withdrawing all anti-inflammatory treatment for the duration of the study. Participants received 1 month of daily simvastatin and 1 month of daily placebo in a randomized, double-blind crossover trial. A total of 16 patients completed per protocol. Asthmatic inflammation was evaluated by measuring exhaled tidal nitric oxide, alveolar nitric oxide, sputum and peripheral eosinophil count, methacholine hyperresponsiveness, salivary eosinophilic cationic protein, and C-reactive protein. Measurements of dynamic and static lung volumes and of cholesterol were also made. RESULTS: After initial withdrawal of usual asthma medication, there was a 1.43 geometric mean fold increase (ie, 43% difference) in fraction of exhaled nitric oxide (95% CI, 1.15 to 1.78; P = .004). Compared with placebo, simvastatin led to a 0.86 geometric mean fold decrease (95% CI, 0.7 to 1.04; P = .15) in exhaled nitric oxide (ie, a 14% difference), and a -0.18 doubling dilution shift (95% CI, -1.90 to 1.55; P = 1.0) in methacholine hyperresponsiveness. There were no significant differences in other inflammatory outcomes, lung volumes, or airway resistance between simvastatin and placebo. Treatment with simvastatin led to a significant reduction (P < .005) of total and low-density lipoprotein cholesterol. CONCLUSION: There is no evidence to suggest simvastatin has anti-inflammatory activity in patients with asthma. CLINICAL IMPLICATIONS: Simvastatin is not useful for the treatment of asthma.     

Role of prostaglandin D2 and E2 terminal synthases in chronic rhinosinusitis

BACKGROUND: Prostaglandin (PG)D(2) and E(2), two major cyclooxygenase (COX) products, are generated by PGD(2) synthase (PGDS) and PGE(2) synthase (PGES), respectively, and appear to mediate airway inflammation. OBJECTIVE: We sought to determine the role of PGDS and PGES in the pathophysiology of chronic rhinosinusitis (CRS). METHODS: The study examined the expression of PGDS and PGES in nasal polyps of 22 CRS patients. As controls, uncinate process mucosae were obtained from 12 CRS patients not having nasal polyps and five subjects without sinusitis. Immunohistochemistry and quantitative real-time PCR were used to evaluate the expression. RESULTS: Both PGDS and PGES were detected in nasal polyps by immunohistochemistry. Significantly greater levels of PGDS mRNA and lesser levels of PGES mRNA were observed in the nasal polyps as compared with uncinate process mucosae, and an inverse correlation between PGDS and PGES expression was observed. Levels of PGDS mRNA in nasal polyps were positively correlated with degree of infiltration by EG2+ eosinophils, whereas the levels of PGES were inversely correlated. Significantly increased levels of PGDS and conversely decreased levels of PGES were observed in asthmatics as compared with non-asthmatics. In addition, PGDS and PGES levels were positively and inversely correlated with the radiological severity of sinusitis, respectively. CONCLUSIONS: These results suggest that PGDS and PGES display an opposite and important role in the pathophysiology of CRS such as polyp formation, and more specifically, a biased expression of these synthases might contribute to the development of CRS by affecting eosinophilic inflammation.     

The use of exhaled nitric oxide concentration to identify eosinophilic airway inflammation: an observational study in adults with asthma

BACKGROUND: Assessment of eosinophilic airway inflammation may be helpful in the management of asthma. Nitric oxide (NO) has potential advantages as a tool to monitor airway inflammation although little is known about the relationship between NO and eosinophilic airway inflammation and the factors which influence it. METHODS: We set out to define the relationship between exhaled NO and the sputum eosinophil count, identify the exhaled NO concentration that best identified a sputum eosinophil count >3% and investigate the impact of several potential confounding factors in 566 consecutive patients with varying severity of asthma. Finally we examined the ability of exhaled NO concentrations measured at differing exhalation flows to identify the presence of a sputum eosinophilia. RESULTS: We found a significant positive relationship between exhaled NO and sputum eosinophil count (R(2)=0.26, P<0.001) which was best described using a non-linear model. There were no clinically important confounding factors to this model. In non-smokers an exhaled NO concentration of >8.3 p.p.b. at 250 mL/s gave 71% sensitivity and 72% specificity for identifying a sputum eosinophil count of >3%. CONCLUSIONS: This value of exhaled NO would seem to be the best for identifying significant eosinophilic airway inflammation. It is applicable to a wide range of non-smoking patients with asthma; exhalation flow does not alter the ability of exhaled NO concentration to detect a sputum eosinophilia.     

United airways again: high prevalence of rhinosinusitis and nasal polyps in bronchiectasis

Background: Although various relationships between the lower and upper airways have been found, the association of bronchiectasis with chronic rhinosinusitis and nasal polyps has not been thoroughly evaluated. This study was undertaken to examine the association of idiopathic and postinfective bronchiectasis with chronic rhinosinusitis and nasal polyposis. Methods: In a prospective study, 56 patients with idiopathic and 32 with postinfective bronchiectasis were evaluated for chronic rhinosinusitis and nasal polyposis by using EP³OS criteria and assessing: symptoms score, nasal endoscopy, sinonasal and chest CT scan, nasal and lung function and nasal and exhaled NO. Results: Most bronchiectasis patients (77%) satisfied the EP³OS criteria for chronic rhinosinusitis, with anterior (98.5%) and posterior (91%) rhinorrhea and nasal congestion (90%) being the major symptoms. Patients presented maxillary, ethmoidal and ostiomeatal complex occupancy with a total CT score of 8.4 ± 0.4 (0–24). Using endoscopy, nasal polyps with a moderate score of 1.6 ± 0.1 (0–3) were found in 25% of patients. Nasal NO was significantly lower in patients with nasal polyposis (347 ± 62 ppb) than in those without them (683 ± 76 ppb; P < 0.001), and inversely correlated (R = ?0.36; P < 0.01) with the ostiomeatal complex occupancy. In the chest CT scan, patients with chronic rhinosinusitis showed a higher bronchiectasis severity score (7.2 ± 0.5; P < 0.001) than patients without (3.7 ± 0.7). The prevalence of chronic rhinosinusitis, nasal polyps and other outcomes were similar in idiopathic and postinfective bronchiectasis. Conclusions: The frequent association of chronic rhinosinusitis and nasal polyposis with idiopathic and postinfective BQ supports the united airways concept, and it suggests that the two type of bronchiectasis share common etiopathogenic mechanisms.     

Granule core loss in eosinophils from a patient with aspirin-induced asthma: an electron microscopic study

Aspirin and other antiinflammatory drugs except steroid hormones precipitate asthmatic attacks in some patients with nasal polyps. The respiratory reaction can be severe and life-threatening. The incidence of nasal polyp found in aspirin-induced asthma ranges from 60% to 100%. This case report concerns a 27-year-old Japanese man who has suffered from asthma for 4 years and had attacks of asthma after ingestion of antipyretics. He had nasal polyps and sinusitis. The polyps were removed and examined electron microscopically. The most conspicuous finding was the disappearance of crystalloid electron-dense cores in granules of most eosinophils, although the amorphous matrix of the granules remained.     

UBE3C genetic variations as potent markers of nasal polyps in Korean asthma patients

The human ubiquitin protein ligase E3C (UBE3C) regulates airway inflammatory responses and is hypothesized to be associated with the presence of nasal polyps in asthma-related diseases. A total of 24 UBE3C single-nucleotide polymorphisms (SNPs) were genotyped in a 467 Korean asthma cohort that was stratified into more homogenous phenotypes of 114 aspirin-exacerbated respiratory disease subgroup and 353 aspirin-tolerant asthma (ATA) subjects. Association analysis revealed that 16 UBE3C SNPs were significantly associated with presence of nasal polyps in the overall asthma group (P=0.0008 and P(corr)=0.01; odds ratio (OR)=0.60). The strength of association from 10 polymorphisms was increased in the ATA subgroup (P=0.0002 and P(corr)=0.003; OR=0.49). In addition, UBE3C_ht1 was found to be consistently associated with nasal polyps in the overall asthmatics group (P=0.006) and the ATA phenotype (P=0.002; P(corr)=0.02) via a codominant mechanism. Our findings provide evidence that variations in UBE3C are potent genetic markers of nasal polyps development in Korean asthmatics and may contribute novel insights into the clinical relevance and potential involvement of UBE3C in respiratory deficiencies.     

Smoking, environmental tobacco smoke, and aspirin-exacerbated respiratory disease

BackgroundTobacco smoke is a widely recognized environmental pollutant and is a major public health hazard worldwide. Although environmental tobacco smoke (ETS) has a clear link with many conditions, including asthma, ear infections, and sinus cancer, evidence related to aspirin-exacerbated respiratory disease (AERD) requires further investigation.ObjectiveTo investigate whether active smoke or ETS exposures are associated with an increased risk of developing AERD.MethodsA total of 260 patients with AERD were enrolled in a case-control study with their respective asymptomatic spouses serving as matched controls. Multiple logistic regression analysis was used to examine the association of AERD with active smoking and ETS, adjusted for age, sex, and location of childhood residence.ResultsThe AERD case patients were more likely to have ever smoked actively when compared with controls (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.04-2.28). A significant association (OR, 3.46; 95% CI, 2.22-5.39) was found between childhood ETS exposure and AERD. If a patient was exposed to ETS during both childhood and adulthood, results showed an OR of 5.09 for developing AERD (95% CI, 2.75-9.43). However, no statistically significant association between AERD and ETS only during adulthood was found (OR, 1.60; 95% CI, 0.75-3.40), suggesting that the combined effect of childhood and adulthood ETS may be augmented by the prior childhood exposure.ConclusionsActive smoking and childhood ETS exposure are associated with increased odds of developing AERD. In particular, combined childhood and adulthood exposure had major effects. This study suggests that ETS is at least one contributor to the syndrome of AERD.