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.

The minimal clinically important difference in allergic rhinitis.

BACKGROUND: When presented with results from clinical measurements or research findings, clinicians must first make an interpretation of their importance, not only in statistical terms, but also the 'clinical importance' given the size of the change observed. To do this, they require an understanding of the relationship between their outcome measures, and the patient's perception of change. The minimal clinically important difference (MCID) illustrates this relationship by calculating the smallest change in a given outcome that is meaningful to a patient. There are few reports of calculated MCIDs in the Rhinology literature. OBJECTIVE: To calculate MCIDs for common subjective and objective outcome measures in allergic rhinitis (AR). METHODS: Nine randomized, blinded, placebo-controlled clinical trials in intermittent and persistent AR (pooled subjects, n=204) were analysed using anchor- and distribution-based approaches, applying regression and meta-analysis techniques. RESULTS: MCIDs were obtained for the Mini Rhinoconjunctivitis Quality of Life Questionnaire: 0.4 units, peak nasal inspiratory flow: 5 L/min and total nasal symptoms score: 0.55 units. Nasal NO measurement changes had no correlation with patient perceptions of benefit. CONCLUSION: Estimates of MCIDs were obtained for common subjective and objective rhinological outcomes. MCIDs can and should be applied by physicians interpreting research findings, as well as researchers reporting their findings. We can then be confident that our changes in practice will be of perceptible benefit to the patient.

Posterior tragal perichondrium harvesting for myringoplasty.

We present a modified harvesting approach for tragal perichondrium, used in tympanic membrane reconstruction. The technique described avoids amputation of the targus thereby facilitating dissection of the perichondrium from the cartilage as compared to the traditional method. The approach described is technically easier, and removes any potential for cosmetic deformity associated with tragal cartilage amputation and reimplantation. Furthermore, both the anterior tragal perichondrium and the temporalis fascia remain intact if further surgery is required. We recommend this approach for permeatal, tragal perichondrial grafting of small to medium sized tympanic membrane perforations.

Radiation induced sarcoma of the head and neck.

BACKGROUND: Radiation-induced sarcoma of the head and neck (RISHN) is a long-term complication of treatment. The rarity of this tumour is reflected in the very few series reported in the English language medical literature. The incidence of RISHN is, however, likely to increase due to progressive aging of the population combined with improved survival in head and neck cancer patients resulting from better treatment regimes. Diagnosis and management of this problem can be extremely challenging and the overall outlook has been reported to be very bleak. As survival data from isolated case reports cannot be expected to provide reliable information on outcome, we have reviewed 69 cases reported in the English medical literature since 1966 and pooled this information with our experience in treatment of RISHN. PATIENTS AND METHODS: Ten patients with features of a RISHN were treated at the Royal Marsden Hospital between 1944 and 1997. The features of RISHN, treatment, and outcome were analysed in these patients. Additionally, 61 eligible patients with RISHN reported in the literature between 1966 and 1997 were pooled with nine of our patients to form the RISHN group (n = 70). This group was then compared for survival with 124 patients with a diagnosis of head and neck sarcoma registered on the Head and Neck Sarcoma database at the Royal Marsden Hospital (SHN group). Lifetables were constructed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: There was no site of predilection for RISHN, but malignant fibrous histiocytoma (MFH) was the commonest pathological diagnosis. The period of latency between initial radiation therapy and diagnosis of RISHN ranged from 9 to 45 years with a median of 17 years. Surgery was the mainstay of treatment and follow-up ranged from 6 months to 15 years with a median of 48 months. The actuarial five-year disease free survival in these patients was 60%. CONCLUSION: There is at present little or no prospect for effective prevention of RISHN and therefore, a high index of suspicion based on the patient's symptoms assumes great importance in the outcome of these patients. Although surgical management of RISHN is challenging because of the close proximity of the tumour to important regional structures and the technical difficulties of operating in an irradiated area, complete surgical excision appears to offer the best means for palliation and the only realistic chance for long-term survival.

Methadone-related overdose deaths in South Australia, 1984-1994. How safe is methadone prescribing?

OBJECTIVE: To assess the safety of prescribing of methadone tablets and syrup in South Australia by investigating overdose deaths of patients using prescribed methadone and non-patients using illegally obtained methadone. DESIGN: Surveillance study of deaths related to methadone overdose, 1984-1994. DATA SOURCES: Coroner's Office and the Therapeutic Goods Section of the South Australian Health Commission. RESULTS: Per capita prescription of methadone tablets for chronic pain in South Australia was the highest in Australia in 1994. A large increase in deaths, due mainly to methadone tablets prescribed for chronic pain, occurred in 1993-1994. Illegal diversion of methadone to non-patients was responsible for half of the deaths during these two years. Deaths from overdoses of methadone syrup prescribed in maintenance therapy for drug dependence declined from 1984 to 1994. The relative risk for patient deaths due to methadone tablets versus methadone syrup was estimated to be 7.29 (95% confidence limits, 2.15-31.48). Psychotropic drug combinations were present in 86% of deaths. CONCLUSION: The methadone syrup program for drug dependence remains relatively safe. Our data raise concerns about prescribing methadone tablets for chronic pain. Better prescriber education and accountability, patient assessment and supervision and advice to patients about concurrent use of alcohol and benzodiazepines are needed.

Topical gentamicin-induced hearing loss: a mitochondrial ribosomal RNA study of genetic susceptibility.

Mitochondrial ribosomal RNA mutation has been shown to predispose affected individuals to aminoglycoside-induced hearing loss (AIHL). An A-to-G nucleotide substitution at the 1555 position within the 12S ribosomal RNA gene has been identified with a maternally inherited pattern in affected Asian pedigrees. The aim of this study was to identify the frequency of this DNA polymorphism in subjects who appear to show hypersensitivity to topical (middle ear) application of aminoglycoside. In this pilot study, 10 subjects with AIHL were recruited. Eight underwent vestibular ablative therapy with middle ear instillation of gentamicin for disabling vertigo, and two were treated with topical antibiotic drops for otitis media in the presence of a tympanic perforation. DNA samples were extracted, and polymerase chain reaction (PCR) technique was used for gene amplification and purification, searching for 1555 A-to-G substitution in the 12S ribosomal RNA gene. None of the subjects demonstrated this specific mutation.

Punctate diathermy of the soft palate: a new approach in the surgical management of snoring.

We present our experiences in the surgical management of 21 snorers, utilizing a new approach designed to stiffen the palatal musculature, without compromising its function. This was achieved by using a punctate pattern of intrapalatal diathermy to achieve fibrosis within the palate and hence the requisite stiffening. The initial results of this procedure are encouraging showing a subjective improvement in snoring in 85.7 per cent of patients and an increase in sleeping in the same room as their partner every night, from 14.3 per cent pre-operatively to 57.1 per cent post-operatively.

Supraglottic transection: results of repair and functional outcome.

We present two cases of supraglottic transection, with concomitant neurotemesis of the superior laryngeal nerve. Both cases were repaired primarily and a temporary tracheostomy was used to protect the airway. In both cases subsequent decannulation was achieved within four weeks, following the initial injury. No long-term swallowing or voice disturbance was noted in either case. We recommend that in such cases it is unnecessary to repair the nerves directly, but that careful repair of the wound itself will achieve a functional result.

Emergency workload in otolaryngology.

A 6-month prospective audit of the otolaryngology emergency workload in a district general hospital was undertaken. A total of 742 cases was referred of whom 193 (26%) were children (< 16 years). The male to female ratio was equal, and 69% of cases were referred from the accident and emergency department. Although most conditions were minor enough to be managed in the ward treatment room and either discharged (40%) or followed up as outpatients (27%), more than one-quarter of patients (28%) needed management by a post-fellowship ENT surgeon. Of the patients, 31% (230/742) were admitted, of whom 107 (46%) required an operation under general anaesthesia. The consequent ENT emergency workload represented 24% of all new patient referrals, 20% of ENT ward admissions and 10% of ENT surgical procedures.

Respiratory symptoms, immunological responses, and aeroallergen concentrations at a sawmill.

After identification of a case of extrinsic allergic alveolitis due to exposure to wood dust at a sawmill, all employees at the sawmill where he worked were studied with an occupational, environmental, and symptom questionnaire, spirometry, skin prick tests, and serum specific IgG measurements. Ninety five of current and 14 of 17 ex-sawmill workers were studied. As a basis for comparison, a group of 58 workers from a nearby light engineering factory were also studied. Few women (6) were employed and they were excluded from the analysis. Workers at the sawmill were stratified into high and low exposure groups depending on their place of work. This division was supported both by their subjective assessment of the dustiness of their environment and the results of personal dust samples. There were no significant differences between the three groups in age, height, smoking habits, exposure to other causes of extrinsic allergic alveolitis, forced expiratory volume in one second, forced vital capacity, atopic state, or cutaneous reactivity to moulds. In the high exposure group the prevalence of work related cough and nasal and eye symptoms was higher than in the low exposure and comparison groups. The prevalence of work related wheeze was similar in both the high exposure and comparison groups, but was lower in the low exposure group. The prevalences of chronic bronchitis and symptomatic bronchial hyper-reactivity were similar in the high and low exposure groups but were lower in the comparison group. Serum concentrations of specific IgG against extracts of sawdust and Trichoderma koningii were significantly higher in the high exposure group than in the other two groups. The prevalence of symptoms suggestive of extrinsic allergic alveolitis was 4.4% in the high exposure group, greater than in the low exposure group (0%), and the comparison group (1.9%). In conclusion extrinsic allergic alveolitis probably occurs in British sawmills, and among the exposed population its prevalence may be as high as that reported in Sweden. The allergen responsible is likely to be from mould growing on the wood and may be from Trichoderma koningii.

Blood carbonmonoxyhaemoglobin levels are chronically elevated in alcoholics treated for detoxification.

Self-reported daily consumption of cigarettes and ethanol was recorded from a group of 59 ethanol-dependent persons admitted to a detoxification clinic at 2000-2400 h and averaged 40 cigarettes per day and 320 g ethanol per day, respectively. In consequence, concentrations of blood COHb and ethanol were high. Mean values for COHb were 8.5 and 9.9% in men and women, respectively, while the corresponding levels for ethanol were 220 and 280 mg/100 ml. Blood acetate concentrations were also elevated and correlated negatively with mixed venous oxygenhaemoglobin concentrations. The mean carbonmonoxyhaemoglobin concentration at 0700 h was found to be approximately 65% of that on admission. Biochemical and haematological analysis, past medical history and current physical examination revealed a high degree of ethanol and/or cigarette-related pathology. Studies on lipid and lipoprotein metabolism in ethanol-dependent persons should take into account their simultaneous high cigarette abuse.