Airway dysfunction in nasal polyposis: a spectrum of asthmatic disease?

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an interesting model to investigate the existence of a non-allergic unified airway. The factors associated with airway dysfunction in CRSwNP are not fully understood. OBJECTIVE: To assess the impact of nasal disease on lower airway dysfunction in CRSwNP. METHODS: Fifty-seven patients with CRSwNP underwent spirometry, nasal endoscopy, exhaled nitric oxide, methacholine bronchial challenge, blood sampling for total IgE, eosinophil count and radioallergosorbent testing (NCT00788749). Three phenotypic groups were identified: 'asthma group' (asthma diagnosis); 'inflammatory group' [no asthma diagnosis, but elevated fractionated exhaled nitric oxide (FE(NO)) and/or bronchial-hyperreactivity (BHR)]; and 'non-inflammatory group' (no asthma diagnosis, no BHR and normal FE(NO)). Group comparisons, univariate and multivariate analyses were performed to examine associations with airway dysfunction. RESULTS: FEV(1) and FEF(25-75%) were reduced in asthma, but there was no difference between the non-asthmatic groups. Total IgE and eosinophils were elevated in asthma vs. the non-inflammatory group, but there was no difference for asthma vs. inflammatory groups. BHR was the only significant predictor of FEV(1) (P<0.001). For FEF(25-75), BHR and eosinophil count were independent predictors (P<0.001 and P=0.04). Nasal outcomes were not predictors of spirometry. CONCLUSION AND CLINICAL RELEVANCE: In CRSwNP there is asymptomatic airway dysfunction suggestive of an asthmatic phenotype. Impairment of lung function is significantly associated with BHR and eosinophilia but not parameters of nasal disease suggesting that severity of airway dysfunction relates to the spectrum of asthma rather than rhinosinusitis. Lower airway dysfunction is common in CRSwNP but does not correlate to the severity of nasal disease. Signs and symptoms of asthma should be sought and treated in CRSwNP.

Supervised step-down of inhaled corticosteroids in the community--an observational study.

INTRODUCTION: Current asthma guidelines recommend step-down of inhaled corticosteroids (ICS) to the minimum dose required for control of symptoms. AIM: To determine if supervised step-down of (ICS) in the community has any effect on asthmatic inflammation. METHODS: 119 Community based asthmatics underwent progressive step-down of therapy until they became unstable or reached an (ICS) dose of ≤200 µg beclomethasone dipropionate (BDP) or equivalent. Once unstable, participants stepped back up to the last stable dose of ICS. Exhaled nitric oxide (NO) and mannitol challenge were performed at the start and end of step-down. Asthma Quality of Life Questionnaire (AQLQ) and spirometry were recorded at each step-down visit. RESULTS: The median (interquartile range) BDP equivalent dose was significantly higher pre vs. post step-down: 400 µg (400-800) and 250 µg (200-400) per day respectively (P < 0.05). Examination of change in PD(10) in individual patients revealed that 34% had an improvement (>+1 dd), 47% had no change (±-1 dd), and 19% had a worsening (<-1 dd). The geometric mean fold ratio in NO for pre vs. post was 0.96 (95% CI 0.87 to 1.06, P = 0.43). Mean (SEM) values for FEV(1) were 86.2% (1.51) vs. 84.5% (1.46) (P = 0.04). There was a significant improvement in AQLQ. CONCLUSIONS: We have demonstrated that a significant reduction in ICS dose may be achieved in a community setting without any worsening of airways inflammation or lung function, and with an associated improvement quality of life in the majority of patients. This apparent disconnect may reflect enhanced adherence due to supervision of step-down.

Disconnect between standardized field-based testing and mannitol challenge in Scottish elite swimmers.

BACKGROUND: Elite swimmers have high rates of rhinoconjunctivitis and exercise-induced bronchoconstriction. Moreover, exposure to chlorine and chlorine metabolites is known to induce bronchial hyper-reactivity. OBJECTIVE: To assess the early and late effects of chlorine and exercise on the unified airway of elite swimmers, and to compare the response to mannitol and field-based exercise challenge. METHODS: The Scottish national squad underwent exhaled tidal (FE(NO)) and nasal (N(NO)) nitric oxide measurement, peak nasal inspiratory flow (PNIF), and forced expiratory volume in 1 s before, immediately after, and 4-6 h post-swimming. A sport-specific exercise test was carried out during an intensive lactate set (8 min at >/=80% maximum hear rate). All swimmers underwent mannitol challenge, and completed a health questionnaire. RESULTS: N=61 swimmers were assessed: 8/59 (14%) of swimmers had a positive mannitol challenge. Nine out of 57 (16%) of swimmers had a positive exercise test. Only one swimmer was positive to both. Swimmers with a positive mannitol had a significantly higher baseline FE(NO) (37.3 vs. 18.0 p.p.b., P=0.03) than those with a positive exercise challenge. A significant decrease in FE(NO) was observed pre vs. immediate and delayed post-chlorine exposure: mean (95% CI) 18.7 (15.9-22.0) p.p.b. vs. 15.9 (13.3-19.1) p.p.b. (P<0.01), and 13.9 (11.5-16.7) p.p.b. (P<0.01), respectively. There were no significant differences in N(NO.) Mean PNIF increased from 142.4 L/min (5.8) at baseline to 162.6 L/min (6.3) immediately post-exposure (P<0.01). Delayed post-exposure PNIF was not significantly different from pre-exposure. CONCLUSIONS: No association was found between mannitol and standardized field-based testing in elite swimmers. Mannitol was associated with a high baseline FE(NO); however, exercise/chlorine challenge was not. Thus, mannitol may identify swimmers with a 'traditional' inflammatory asthmatic phenotype, while field-based exercise/chlorine challenge may identify a swimmer-specific bronchoconstrictor response. A sustained fall in FE(NO) following chlorine exposure suggests that a non-cellular, perhaps neurogenic, response may be involved in this group of athletes.

Effects of chlorine and exercise on the unified airway in adolescent elite Scottish swimmers.

BACKGROUND: Chlorine metabolites and high training load may produce exercise-induced bronchospasm (EIB) in elite swimmers. The aim of this study was to assess the combined effects of chlorine and exercise on the unified airway of adolescent elite swimmers. METHODS: The Scottish Midlands District squad were assessed during an indoor pool session at the National Swimming Academy. Athletes trained at least 8 h per week. Subjects underwent tidal (T(NO)) and nasal (N(NO)) exhaled NO and peak nasal inspiratory flow (PNIF) pre and post a 2 h session. A physiological exercise challenge assessed EIB in n = 36 swimmers (>10% fall in forced expiratory volume in 1 s (FEV(1))). RESULTS: Combined and free chlorine levels (mg/l) were 1.66 and 0.3 respectively. n = 36 swimmers (mean age 13.3 years) were assessed: n = 8 (22%) had known asthma; n = 13 (36%) had a positive physiological challenge; 18 (50%) complained of symptoms suggestive of EIB. n = 10/28 (36%) who did not have asthma were found to have a positive exercise challenge. There was no significant association between reported exercise symptoms and positive exercise test. There was no significant change in T(NO) or N(NO) for pre vs postexposure, irrespective of asthma diagnosis or AHR. n = 15 (42%) swimmers complained of worsening nasal symptoms postexposure, but only n = 7 (14%) had a demonstrable fall in PNIF (mean 33 l/min). No significant association was found between PNIF and symptoms. CONCLUSIONS: Combined exposure to chlorine and exercise did not affect surrogate markers of inflammation in the unified airway. There was a high prevalence of undiagnosed EIB.

Steroid sparing effects of intranasal corticosteroids in asthma and allergic rhinitis.

BACKGROUND: Treating allergic rhinitis may have a downstream anti-inflammatory effect on the lower airways. We conducted a dose ranging study in asthma and persistent allergic rhinitis to evaluate if intranasal corticosteroids exhibit a sparing effect on the dose of inhaled corticosteroid. METHODS: Twenty five participants were randomized to receive two weeks of 100 microg/day (Low dose) or 500 microg/day (High dose) of inhaled fluticasone propionate both with intranasal placebo; or inhaled fluticasone 100 microg/day with intranasal fluticasone 200 microg/day (Combined) in a double-blind cross-over fashion. RESULTS: Low dose fluticasone produced a shift of 1.20 doubling-dilutions (95% CI, 0.63, 1.77); Combined fluticasone, 1.79 doubling-dilutions (95% CI, 0.77, 2.80) and high dose fluticasone, 2.01 doubling-dilutions (95% CI, 1.42, 2.61) in methacholine PC(20) from respective baselines. There was a significant difference between high and low doses: 0.82 doubling dilutions (95%CI, 0.12, 1.50) but not between combined and low dose 0.58 doubling dilutions (95% CI, -0.78, 1.95). Combined treatment alone produced improvements in peak nasal inspiratory flow (P < 0.001), rhinitis quality of life (P = 0.004) and nasal NO (P = 0.01); reduced blood eosinophil count (P = 0.03), and serum eosinophil cationic protein (P = 0.02). All treatments significantly improved tidal NO, FEV(1) and asthma quality of life. CONCLUSIONS: High-dose fluticasone was superior to low dose fluticasone for methacholine PC20, demonstrating room for further improvement. Combined treatment was not significantly different from low dose fluticasone and we could not demonstrate a steroid sparing effect on methacholine PC20. Combined treatment alone produced improvements in upper airway outcomes and suppressed systemic inflammation but not adrenal function.