Vascularity in asthmatic airways: relation to inhaled steroid dose

BACKGROUND: There is an increase in vascularity in the asthmatic airway. Although inhaled corticosteroids (ICS) are an effective anti-inflammatory treatment in asthma, there are few data on any effects on structural changes. METHODS: Endobronchial biopsy specimens from seven asthmatic subjects not receiving ICS and 15 receiving 200-1500 microg/day beclomethasone dipropionate (BDP) were immunohistochemically stained with an anti-collagen type IV antibody to outline the endothelial basement membrane of the vessels. These were compared with biopsy tissue from 11 non-asthmatic controls (four atopic and seven non-atopic). RESULTS: There was a significant increase in the density of vessels (number of vessels/mm2 of lamina propria) in the asthmatic subjects not on ICS compared with non-asthmatic controls (mean 485 (interquartile range (IQR) 390-597) versus 329 (IQR 248-376) vessels/mm2, p<0.05; 95% CI for the difference 48 to 286). There was no significant difference between asthmatic subjects on ICS and those not on ICS or control subjects in the number of vessels/mm2 (mean 421 (IQR 281-534)). However, patients who received >/=800 microg/day BDP tended to have a reduced number of vessels/mm2 compared with patients not on ICS and those receiving 相似文献   

Minor head injury: predicting follow-up after discharge from the Emergency Department

Background : Up to 50% of ED patients discharged within a minor head injury (MHI) will develop postconcussive syndrome (PCS) within 1 month of injury. The follow-up visit is an important opportunity to identify and treat PCS before it becomes persistent. _wi Objective : To identify factors predictive of follow-up (FU) after ED discharge in patients presenting th MHI. Methods : Prospective, observational study of a convenience sample of 71 MHI presenting within 24 hours of injury to the ED of a university teaching hospital between February 1996 and October 1997. MHI defined as loss of consciousness not greater than 10 minutes or amnesia, GCS 15, no skull fracture on PE, no new focality to neurologic exam and no brain injury on CT if one was done. Neurobehavioural test scores, clinical information and demographic data collected via use of standardized patient encounter form. All patients were discharged with written instructions to FU with their private physician within 1-2 weeks. Patients without a follow-up physician were assigned one. At 1 month post-injury, all patients were telephoned to determine if they had followed-up. Analysis : Stepwise, multivariate, logistic regression. Results : Thirty one out of 71 (43.7%) reported FU with a physician within 1 month. Factors associated with FU were performance of a head CT in the ED (OR = 3.58, 95% CI = 1.12- 11.37), associated laceration (OR = 8.84, 95% CI = 1.69-42.55), female gender (OR = 3.19, 95% CI = 1.04-9.82), and African-American race (OR = 0.36, 95% CI = 0.13-0.99). Conclusions : Several factors predict FU after ED discharge for MHI. Patients unlikely to FU may benefit from an assessment of PCS risk before they leave the ED.     

Case-control study of severe life threatening asthma (SLTA) in a developing community

BACKGROUND: Distinct risk factors for asthma death have not been identified in developing communities. This study was conducted to distinguish risk factors for severe life threatening asthma (SLTA), a proxy for asthma death, in a developing country. METHODS: A case-control study was performed at a University Hospital serving developing communities in the Western Cape Province, South Africa, over the period October 1997 to April 2000. Thirty consecutive patients with SLTA admitted to the intensive care unit (ICU) were compared with 60 chronic asthmatic patients, without a history of SLTA, who had attended the hospital outpatient respiratory clinic over the same period. RESULTS: The risk of SLTA in comparison with controls increased with female sex (odds ratio (OR) 3.3, 95% CI 1.2 to 9.6, p = 0.02), rural residence (OR 8.1, 95% CI 2.6 to 25.3, p = 0.0005), and absence of a formal income (OR 5.7, 95% CI 2 to 16.6, p = 0.002). Cases were more likely to have had more than one hospital admission in the previous year (OR 8, 95% CI 2.5 to 25.2, p = 0.0009) and more than one emergency room visit in the previous year (OR 4.4, 95% CI 1.19 to 16.4, p = 0.04). Patients with SLTA were less likely to use inhaled corticosteroids (OR 5.6, 95% CI 1.9 to 16.5, p = 0.003) and more likely to use inhaled fenoterol (OR 6, 95% CI 2.2 to 16.2, p = 0.0004). Patients with SLTA also had lower mean (SE) forced expiratory volume in 1 second (FEV(1)) measurements (66.9 (9.5)% predicted v 82.5 (4.0)% predicted; p = 0.03) and lower FEV1/FVC ratios (60.7 (4.1)% predicted v 69.6 (1.9)% predicted; p = 0.05) documented before the episode of SLTA. CONCLUSIONS: Risk factors for SLTA that are mainly analogous to those distinguished in other environments have been identified in a geographical area characterised by a third world socioeconomic context. Rural residence and poverty may increase the risk of SLTA.     

Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma

BACKGROUND: Inhaled corticosteroids are effective at preventing asthma morbidity and mortality. Most studies, however, have focused on short term effects, raising uncertainty about their effectiveness in the long term. METHODS: The Saskatchewan Health databases were used to form two population based cohorts of asthma patients aged 5-44 between 1975 and 1991. The first cohort included all subjects from the start of asthma treatment, while the second included subjects hospitalised for asthma from the date of discharge. Subjects were followed up, starting 1 year after cohort entry and continuing until 1997, 54 years of age, or death. The outcome was the first asthma hospital admission and readmission, respectively, to occur during follow up. A nested case-control design was used by which all cases were matched on calendar time and several markers of asthma severity to all available controls within the cohort. RESULTS: The full cohort included 30 569 asthmatic subjects of which 3894 were admitted to hospital for asthma and 1886 were readmitted. The overall rate of asthma hospitalisation was 42.4 per 1000 asthma patients per year. Regular use of inhaled corticosteroids was associated with reductions of 31% in the rate of hospital admissions for asthma (95% confidence interval (CI) 17 to 43) and 39% in the rate of readmission (95% CI 25 to 50). The rate reduction found during the first 4 years of follow up was sustained over the longer term. Regular use of inhaled corticosteroids can potentially prevent between five hospital admissions and 27 readmissions per 1000 asthma patients per year. CONCLUSION: Regular use of low dose inhaled corticosteroids prevents a large proportion of hospital admissions with asthma, both early and later on in the course of the disease.     

The prevalence of aspirin intolerant asthma (AIA) in Australian asthmatic patients

BACKGROUND: Aspirin intolerant asthma (AIA) is a clinically distinct syndrome characterised by the precipitation of asthma attacks following the ingestion of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). The prevalence of AIA among Australian asthmatic patients has not previously been reported. METHODS: Three populations were surveyed to establish the prevalence of AIA among Australian asthmatics. Two surveys were completed in patients recruited from the metropolitan area in Perth, Western Australia, one comprising 150 recruited from hospital based sources (hospital cohort) and the second comprising 366 from the membership of the Asthma Foundation of Western Australia (Asthma Foundation cohort). In a third study 1298 individuals were randomly selected from the rural community of Busselton in Western Australia. RESULTS: The prevalence of AIA in the hospital and Asthma Foundation cohorts was found to be 10.7% and 10.4%, respectively. Univariate analyses in the Asthma Foundation cohort indicated that AIA was associated with more severe asthma (OR = 2.4, 95% CI 1.18 to 4.86), nasal polyposis (OR=3.19, 95% CI 1.52 to 6.68), atopy (OR=2.96, 95% CI 1.48 to 5.89), sulfite sensitivity (OR=3.97, 95% CI 1.87 to 8.41), and sensitivity to wine (OR=3.27, 95% CI 1.65 to 6.47). Multivariate analyses indicated that atopy (OR=2.80, 95% CI 1.38 to 5.70), nasal polyposis (OR=3.39, 95% CI 1.57 to 7.29), and the number of asthma attacks in the previous 12 months (OR=1.20, 95% CI 1.02 to 1.42) were independent predictors for AIA, as was wine sensitivity (OR=2.20, 95% CI 1.02 to 4.72). The prevalence of AIA among asthmatic patients in the Busselton cohort was 10.9%. In addition, 2.5% of non-diagnosed asthmatics in this cohort reported asthma symptoms following aspirin ingestion. CONCLUSION: The prevalence of respiratory symptoms triggered by aspirin/NSAID use was found to be 10-11% in patients with asthma and 2.5% in non-asthmatics. Aspirin sensitivity appears to be a significant problem in the community and further investigations of the mechanisms of these responses and the possible link between this syndrome and other food and chemical sensitivities are required.     

A randomised trial of self-management planning for adult patients admitted to hospital with acute asthma

BACKGROUND: There is still debate over the benefit of self-management programmes for adults with asthma. A brief self-management programme given during a hospital admission for acute asthma was tested to determine whether it would reduce readmission. METHOD: A randomised controlled trial was performed in 280 adult patients with acute asthma admitted over 29 months. Patients on the self-management programme (SMP) received 40-60 minutes of education supporting a written self-management plan. Control patients received standard care (SC). RESULTS: One month after discharge SMP patients were more likely than SC patients to report no daytime wheeze (OR 2.6, 95% CI 1.5 to 5.3), no night disturbance (OR 2.0, 95% CI 1.2 to 3.5), and no activity limitation (OR 1.5, 95% CI 0.9 to 2.7). Over 12 months 17% of SMP patients were re-admitted compared with 27% of SC patients (OR 0.5, 95% CI 0.3 to 1.0). Among first admission patients, OR readmission (SMP v SC) was 0.2 (95% CI 0.1 to 0.7), p<0.01. For patients with a previous admission, OR readmission was 0.8 (95% CI 0.4 to 1.6), p=0.6. SMP patients were more likely than SC patients to be prescribed inhaled steroids at discharge (99% v 92%, p=0.03), oral steroids (98% v 90%, p=0.06), and to have hospital follow up (98% v 84%, p<0.01) but adjustment for these differences did not diminish the effect of the self-management programme. CONCLUSIONS: A brief self-management programme during hospital admission reduced post discharge morbidity and readmission for adult asthma patients. The benefit of the programme may have been greater for patients admitted for the first time. The programme also had a small but significant effect on medical management at discharge.     

Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol

BACKGROUND: The homozygous presence of the arginine-16 variant of the beta(2) adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting beta(2) agonists in asthmatic adults compared with the homozygous glycine-16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting beta(2) agonists. METHODS: A cross-sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004-5. The primary outcome measure was asthma exacerbations over the previous 6 months. RESULTS: There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95% CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95% CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group. CONCLUSIONS: The arginine-16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response.     

Moderate dose inhaled corticosteroids plus salmeterol versus higher doses of inhaled corticosteroids in symptomatic asthma

BACKGROUND: There is uncertainty as to the dose of inhaled corticosteroids (ICS) at which to start concomitant long acting beta agonist (LABA) treatment in patients with asthma not adequately controlled by ICS alone. METHODS: A meta-analysis was carried out of randomised, double blind clinical trials that compared the efficacy of adding salmeterol to moderate doses of ICS (fluticasone propionate 200 mug/day or equivalent) with increasing the ICS dose by at least twofold in symptomatic adult patients with asthma. The main outcome measures were the number of subjects withdrawn from the study due to asthma and the number of subjects with at least one moderate or severe exacerbation. RESULTS: Twelve studies with a total of 4576 subjects met the inclusion criteria for the analyses. The number of subjects withdrawn due to asthma and with at least one moderate or severe exacerbation was higher in the high dose ICS group (odds ratios 1.58, 95% CI 1.12 to 2.24 and 1.35, 95% CI 1.10 to 1.66, respectively). For the secondary outcome variables (forced expiratory volume in 1 second, morning and evening peak expiratory flow, and daytime beta agonist use) there was significantly greater benefit in the salmeterol group. CONCLUSIONS: This meta-analysis shows that the addition of salmeterol to moderate doses of ICS (fluticasone 200 mug/day or equivalent) in patients with asthma symptomatic at that dose results in significantly greater clinical benefit than increasing the dose of ICS by twofold or more.     

Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood

BACKGROUND: The relationship between infant feeding and childhood asthma is controversial. This study tested the hypothesis that the relation between breast feeding and childhood asthma is altered by the presence of maternal asthma. METHODS: Healthy non-selected newborn infants (n = 1246) were enrolled at birth. Asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on > or = 2 questionnaires at 6, 9, 11 or 13 years. Recurrent wheeze (> or = 4 episodes in the past year) was reported by questionnaire at seven ages in the first 13 years of life. Duration of exclusive breast feeding was based on prospective physician reports or parental questionnaires completed at 18 months. Atopy was assessed by skin test responses at the age of 6 years. RESULTS: The relationship between breast feeding, asthma, and wheeze differed with the presence or absence of maternal asthma and atopy in the child. After adjusting for confounders, children with asthmatic mothers were significantly more likely to have asthma if they had been exclusively breast fed (OR 8.7, 95% CI 3.4 to 22.2). This relationship was only evident for atopic children and persisted after adjusting for confounders. In contrast, the relation between recurrent wheeze and breast feeding was age dependent. In the first 2 years of life exclusive breast feeding was associated with significantly lower rates of recurrent wheeze (OR 0.45, 95% CI 0.2 to 0.9), regardless of the presence or absence of maternal asthma or atopy in the child. Beginning at the age of 6 years, exclusive breast feeding was unrelated to prevalence of recurrent wheeze, except for children with asthmatic mothers in whom it was associated with a higher odds ratio for wheeze (OR 5.7, 95% CI 2.3 to 14.1), especially if the child was atopic. CONCLUSION: The relationship between breast feeding and asthma or recurrent wheeze varies with the age of the child and the presence or absence of maternal asthma and atopy in the child. While associated with protection against recurrent wheeze early in life, breast feeding is associated with an increased risk of asthma and recurrent wheeze beginning at the age of 6 years, but only for atopic children with asthmatic mothers.     

Association of asthma and hay fever with irregular menstruation

BACKGROUND: There is some evidence that asthmatic women are more likely to have abnormal sex hormone levels. A study was undertaken to determine whether asthma and allergy were associated with irregular menstruation in a general population, and the potential role of asthma medication for this association. METHODS: A total of 8588 women (response rate 77%) participated in an 8 year follow up postal questionnaire study of participants of the ECRHS stage I in Denmark, Estonia, Iceland, Norway, and Sweden. Only non-pregnant women not taking exogenous sex hormones were included in the analyses (n = 6137). RESULTS: Irregular menstruation was associated with asthma (OR 1.54 (95% CI 1.11 to 2.13)), asthma symptoms (OR 1.47 (95% CI 1.16 to 1.86)), hay fever (OR 1.29 (95% CI 1.05 to 1.57)), and asthma preceded by hay fever (OR 1.95 (95% CI 1.30 to 2.96)) among women aged 26-42 years. This was also observed in women not taking asthma medication (asthma symptoms: OR 1.44 (95% CI 1.09 to 1.91); hay fever: OR 1.27 (95% CI 1.03 to 1.58); wheeze preceded by hay fever: OR 1.76 (95% CI 1.18 to 2.64)). Irregular menstruation was associated with new onset asthma in younger women (OR 1.58 (95% CI 1.03 to 2.42)) but not in women aged 42-54 years (OR 0.62 (95% CI 0.32 to 1.18)). The results were consistent across centres. CONCLUSIONS: Younger women with asthma and allergy were more likely to have irregular menstruation. This could not be attributed to current use of asthma medication. The association could possibly be explained by common underlying metabolic or developmental factors. The authors hypothesise that insulin resistance may play a role in asthma and allergy.     

Cross-sectional study on bone density-related sonographic parameters in children with asthma: correlation to therapy with inhaled corticosteroids and disease severity

The aim of this study was to screen asthmatic children for bone density-related sonographic parameters on the calcaneal bone. Findings were correlated to therapy with inhaled corticosteroids (ICS) as well as with asthma severity (AS), concomitance and severity of atopic dermatitis (AD), and rhinitis (AR). We enrolled 173 children with AS1-3 consecutively; 44% (AS1) had not received any ICS medication; 56% (AS2 and -3) received ICS therapy for > or =6 months (medium daily dose, 286 microg fluticasone-proprionate-equivalent/maximum 500 microg); and in addition 38% (n = 65) presented with AD and 66% (n = 115) with AR. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) results were compared to regional normative values of 3299 children obtained with the identical system. ICS-treated children showed a tendency toward reduced age-, weight-, and height-adjusted standard deviation scores (SDS) for SOS compared to children without ICS treatment, which tendency did not reach statistical significance and was not as consistent for BUA (mean of ICS-treated children compared to our controls: SOS-SDS, -0.29/-0.31/-0.30; BUA-SDS, -0.23/-0.17/-0.05). For ICS-treated children, the proportion of patients with BUA and SOS values below -1 SDS was statistically significant higher for age-adjusted BUA and SOS than for children without ICS medication (BUA 15.00% vs. 5.41%; SOS 32.98% vs. 17.56%). However, we cannot differentiate possible negative effects of ICS from influences of the underlying inflammatory disease because higher asthma severity was associated with greater use of ICS medication. Additionally, the higher physical activity of children with less severe asthma can have influenced quantitative ultrasound (QUS) parameters positively, compared to patients with a higher degree of exercise-induced symptoms. For differentiation of possible negative effect of ICS on ultrasonic bone quality and for evaluation of the potentials of the method, further longitudinal QUS assessment of asthmatics receiving a new ICS treatment is needed.     

Airway inflammation in children with difficult asthma: relationships with airflow limitation and persistent symptoms

BACKGROUND: The effective management and development of new treatments for children with difficult asthma requires investigation of the underlying airway pathology and its relationships with persistent symptoms and airflow limitation. METHODS: The density of immunologically distinct inflammatory cells and cells expressing interleukin (IL)-4, IL-5, and RANTES was determined in paraffin-embedded endobronchial biopsy specimens from 27 children with difficult asthma (6-16 years) following treatment with systemic corticosteroids. Eleven non-asthmatic children (7-16 years) acted as controls. Reticular basement membrane (RBM) thickness was also recorded and forced expiratory volume in 1 second (FEV(1)) and exhaled nitric oxide (FE(NO)) measured, the latter in asthmatic children only. RESULTS: RBM thickness was greater in the asthmatic than the control group (median (range) 7.4 (3.1-11.1) v 5.1 (3.5-7.5) microm, p = 0.02). No other significant tissue difference was seen, nor was there a difference between asthmatic subjects with daily symptoms after systemic corticosteroids and those who became asymptomatic. CD4+ T lymphocyte density was higher in asthmatic subjects with persistent airflow limitation (post-bronchodilator FEV(1)<80% predicted) than in those without (9.1 (5.5-13.6) v 3.5 (0.6-34.9)%, p = 0.027). Analysing all asthmatic subjects together, there were negative correlations between CD4+ T lymphocytes and both pre-bronchodilator FEV(1) (r = -0.57 (95% CI -0.79 to -0.23), p = 0.002) and post-bronchodilator FEV(1) (r = -0.61 (95% CI -0.81 to -0.29), p<0.001). There were no significant correlations between FE(NO) and inflammatory cells of any type. CONCLUSION: In children with difficult asthma treated with systemic corticosteroids, persistent airflow limitation is associated with a greater density of CD4+ T lymphocytes in endobronchial biopsy specimens.     

Asthma in preschool children: prevalence and risk factors

BACKGROUND: The prevalence of asthma in children has increased in many countries over recent years. To plan effective interventions to reverse this trend we need a better understanding of the risk factors for asthma in early life. This study was undertaken to measure the prevalence of, and risk factors for, asthma in preschool children. METHODS: Parents of children aged 3-5 years living in two cities (Lismore, n=383; Wagga Wagga, n=591) in New South Wales, Australia were surveyed by questionnaire to ascertain the presence of asthma and various proposed risk factors for asthma in their children. Recent asthma was defined as ever having been diagnosed with asthma and having cough or wheeze in the last 12 months and having used an asthma medication in the last 12 months. Atopy was measured by skin prick tests to six common allergens. RESULTS: The prevalence of recent asthma was 22% in Lismore and 18% in Wagga Wagga. Factors which increased the risk of recent asthma were: atopy (odds ratio (OR) 2.35, 95% CI 1.49 to 3.72), having a parent with a history of asthma (OR 2.05, 95% CI 1.34 to 3.16), having had a serious respiratory infection in the first 2 years of life (OR 1.93, 95% CI 1.25 to 2.99), and a high dietary intake of polyunsaturated fats (OR 2.03, 95% CI 1.15 to 3.60). Breast feeding (OR 0.41, 95% CI 0.22 to 0.74) and having three or more older siblings (OR 0.16, 95% CI 0.04 to 0.71) decreased the risk of recent asthma. CONCLUSIONS: Of the factors tested, those that have the greatest potential to be modified to reduce the risk of asthma are breast feeding and consumption of polyunsaturated fats.     

Association of perioperative hypotension with subsequent greater healthcare resource utilization

Study objectiveDetermine if perioperative hypotension, a modifiable risk factor, is associated with increased postoperative healthcare resource utilization (HRU).DesignRetrospective cohort study.SettingMulticenter using the Optum® electronic health record database.PatientsPatients discharged to the ward after non-cardiac, non-obstetric surgeries between January 1, 2008 and December 31, 2017 with six months of data, before and after the surgical visit.Interventions/ExposurePerioperative hypotension, a binary variable (presence/absence) at an absolute MAP of ≤65-mmHg, measured during surgery and within 48-h after, to dichotomize patients with greater versus lesser hypotensive exposures.MeasurementsShort-term HRU defined by postoperative length-of-stay (LOS), discharge to a care facility, and 30-day readmission following surgery discharge. Mid-term HRU (within 6 months post-discharge) quantified via number of outpatient and emergency department (ED) visits, and readmission LOS.Main results42,800 distinct patients met study criteria and 37.5% experienced perioperative hypotension. After adjusting for study covariates including patient demographics and comorbidities, patients with perioperative hypotension had: longer LOS (4.01 vs. 3.83 days; LOS ratio, 1.05; 95% CI, 1.04–1.06), higher odds of discharge to a care facility (OR, 1.18; 95% CI, 1.12–1.24; observed rate 22.1% vs. 18.1%) and of 30-day readmission (OR, 1.22; 95% CI, 1.11–1.33; observed rate 6.2% vs. 5.0%) as compared to the non-hypotensive population (all outcomes, p < 0.001). During 6-month follow-up, patients with perioperative hypotension showed significantly greater HRU regarding number of ED visits (0.34 vs. 0.31 visits; visit ratio, 1.10; 95% CI, 1.05–1.15) and readmission LOS (1.06 vs. 0.92 days; LOS ratio, 1.15; 95% CI, 1.07–1.24) but not outpatient visits (10.47 vs. 10.82; visit ratio, 0.97; 95% CI, 0.95–0.99) compared to those without hypotension. There was no difference in HRU during the 6-month period before qualifying surgery.ConclusionsWe report a significant association of perioperative hypotension with an increase in HRU, including additional LOS and readmissions, both important contributors to overall medical costs.     

Exhaled nitric oxide predicts asthma relapse in children with clinical asthma remission

BACKGROUND: Nitric oxide in exhaled air (FE(NO)) is a marker of eosinophilic airway inflammation. A study was undertaken to determine whether FE(NO) predicts asthma relapse in asymptomatic asthmatic children in whom inhaled corticosteroids are discontinued. METHODS: Forty children (21 boys) of mean age 12.2 years on a median dose of 400 mug budesonide or equivalent (range 100-400) were included. FE(NO) was measured before and 2, 4, 12, and 24 weeks after withdrawal of steroids. A relapse was defined as more than one exacerbation per month, or need for beta agonist treatment on 4 days per week for at least 2 weeks, or diurnal peak flow variability of >20%. FE(NO) measurements were performed online with an expiratory flow of 50 ml/s. RESULTS: Nine patients relapsed. Two and 4 weeks after withdrawal of steroids geometric mean FE(NO) in children who were about to relapse was higher than in those who did not relapse: 35.3 ppb v 15.7 ppb at 2 weeks (ratio 2.3; 95% CI 1.2 to 4.1; p = 0.01) and 40.8 ppb v 15.9 ppb at 4 weeks (ratio 2.6; 95% CI 1.3 to 5.1). An FE(NO) value of 49 ppb at 4 weeks after discontinuation of steroids had the best combination of sensitivity (71%) and specificity (93%) for asthma relapse. CONCLUSION: FE(NO) 2 and 4 weeks after discontinuation of steroids in asymptomatic asthmatic children may be an objective predictor of asthma relapse.     

Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma

BACKGROUND: There are few data in asthma relating airway physiology, inflammation and remodelling and the relative effects of inhaled corticosteroid (ICS) treatment on these parameters. A study of the relationships between spirometric indices, airway inflammation, airway remodelling, and bronchial hyperreactivity (BHR) before and after treatment with high dose inhaled fluticasone propionate (FP 750 microg bd) was performed in a group of patients with relatively mild but symptomatic asthma. METHODS: A double blind, randomised, placebo controlled, parallel group study of inhaled FP was performed in 35 asthmatic patients. Bronchoalveolar lavage (BAL) and airway biopsy studies were carried out at baseline and after 3 and 12 months of treatment. Twenty two normal healthy non-asthmatic subjects acted as controls. RESULTS: BAL fluid eosinophils, mast cells, and epithelial cells were significantly higher in asthmatic patients than in controls at baseline (p<0.01). Subepithelial reticular basement membrane (rbm) thickness was variable, but overall was increased in asthmatic patients compared with controls (p<0.01). Multiple regression analysis explained 40% of the variability in BHR, 21% related to rbm thickness, 11% to BAL epithelial cells, and 8% to BAL eosinophils. The longitudinal data corroborated the cross sectional model. Forced expiratory volume in 1 second improved after 3 months of treatment with FP with no further improvement at 12 months. PD(20) improved throughout the study. BAL inflammatory cells decreased following 3 months of treatment with no further improvement at 12 months (p<0.05 v placebo). Rbm thickness decreased in the FP group, but only after 12 months of treatment (mean change -1.9, 95% CI -3 to -0.7 microm; p<0.01 v. baseline, p<0.05 v. placebo). A third of the improvement in BHR with FP was associated with early changes in inflammation, but the more progressive and larger improvement was associated with the later improvement in airway remodelling. CONCLUSION: Physiology, airway inflammation and remodelling in asthma are interrelated and improve with ICS. Changes are not temporally concordant, with prolonged treatment necessary for maximal benefit in remodelling and PD(20). Determining the appropriate dose of inhaled steroids only by reference to symptoms and lung function, as specified in current international guidelines, and even against indices of inflammation may be over simplistic. The results of this study support the need for early and long term intervention with ICS, even in patients with relatively mild asthma.     

Adverse effects of oral corticosteroids in relation to dose in patients with lung disease

BACKGROUND: The adverse effects of oral corticosteroids are widely recognised but there are few quantitative data on which to base advice to patients. In a two part cross sectional study we compared adverse effects in patients with lung disease taking oral corticosteroids and control subjects and related the adverse effects to corticosteroid dose in the patient group. METHODS: Data on oral corticosteroid use, lifestyle, fractures, and other possible adverse effects were collected by questionnaire and compared between a community based cohort of patients taking continuous or frequent intermittent oral corticosteroids for asthma, chronic obstructive pulmonary disease, or alveolitis and age and sex matched control subjects. Dose related effects were explored in the corticosteroid group using cumulative dose quartiles and multiple logistic regression. RESULTS: A total of 367 patients (> or = 50 years, 48% female) and 734 control subjects completed the questionnaire. The cumulative incidence of fractures since the time of diagnosis was 23% for patients taking oral corticosteroids and 15% in the control group (odds ratio (OR) 1.8; 95% confidence interval (CI) 1.3 to 2.6). Patients were more likely to have had a fracture of the vertebrae (OR 10; 95% CI 2.9 to 34), hip (OR 6; 95% CI 1.2 to 30), and ribs or sternum (OR 3.2, 95% CI 1.6 to 6.6) than control subjects. They also reported a significant increase in cataracts, use of antacids, muscle weakness, back pain, bruising, oral candidiasis, and having fewer teeth. The effects of oral corticosteroids were dose related: the odds ratio for patients in the highest compared with the lowest cumulative dose quartile (median prednisolone dose 61 g versus 5 g) ranged from 2 for all fractures to 9 for vertebral fractures and bruising. CONCLUSIONS: By quantifying the morbidity associated with the use of oral corticosteroids, this study should help to rationalise their long term use.