Role of symptoms and lung function in determining asthma control in smokers with asthma

Background:  Cigarette smoking in asthma increases the severity and accelerates the decline in lung function. The relative role of symptoms and lung function in determining asthma control in smokers with asthma is not known.
Aim of the study:  The aim of this study was to compare asthma control in smokers vs never-smokers with asthma, using the validated Juniper asthma control questionnaire (ACQ), and assess if any difference was because of a particular symptom or the forced expiratory volume in one second (FEV₁) value.
Methods:  This was a cross-sectional study of 134 asthmatics (74 never-smokers and 60 smokers) with ≥15% reversibility in FEV₁ after salbutamol. All subjects completed the ACQ, recording FEV₁ and asthma symptoms (night awakening, morning symptoms, dyspnoea, wheeze, activity limitation and use of reliever inhaler).
Results:  Compared with the never-smokers, smokers with asthma had significantly worse median (IQR) total asthma control score [1.6 (1.1–2.3) vs 2.8 (1.7–3.4); ( P  < 0.0001)] and in each of the six individual symptom question scores ( P  < 0.001), but no difference in FEV₁ levels ( P  = 0.908).
Conclusion:  Asthma control is significantly worse in asthmatics who smoke compared with never-smokers, with all symptoms related to asthma control uniformly worse in smokers, independent of FEV₁.     

Serum eosinophil cationic protein (ECP) as a marker of disease activity and treatment efficacy in seasonal asthma

This study was carried out to determine whether serum eosinophil cationic protein (ECP) represents a sensitive marker for disease activity in atopic asthmatic patients during the pollen season. The study, in double-blind fashion, was performed between February and June 1994. Two groups of 10 seasonal asthmatic patients randomly received two different treatments. The first group was treated with inhaled beclomethasone dipropionate (BDP) 500 μg bid; the second received a matched placebo (P). At the beginning and every month, blood samples for determination of ECP and eosinophil count were collected and lung function (FEV₁) and methacholine responsiveness (PD₂₀) were performed. Subjects recorded daily symptoms of asthma, salbutamol consumption, and peak expiratory flow (PEF) values. In the P group, all indices, except FEV₁, showed significant changes during the pollen season ( P < 0.001). In the BDP group, significant changes were detected for symptom score ( P < 0.01), salbutamol consumption ( P < 0.01), and eosinophil number ( P < 0.05). Between the two groups, significant differences for symptom score ( P < 0.001), salbutamol consumption ( P < 0.001), ECP levels ( P < 0.05), eosinophil count ( P < 0.02), PD₂₀ methacholine ( P < 0.02), and PEF values ( P < 0.01) were detected. Changes in serum ECP significantly correlated with changes in other parameters ( P < 0.001), except FEV₁. Our results provide evidence that serum ECP is a sensitive marker for monitoring of the disease activity in seasonal asthma. Furthermore, it may offer a useful tool for estimating treatment efficacy.     

Does asthma control correlate with quality of life related to upper and lower airways? A real life study

Background:  The goal of asthma therapy is to achieve an optimal level of disease control, but the relationship between asthma control, impact of comorbid rhinitis and health related quality of life (HRQoL) in real life remains unexplored.
Objective:  The aims of this real life study were to evaluate asthma control, the impact of asthma (with and without rhinitis) on HRQoL, the relationship between asthma control and HRQoL, and the role of rhinitis on asthma control and HRQoL.
Methods:  122 asthma patients completed the Asthma Control Test, Rhinitis Symptoms score (T5SS) and RHINASTHMA.
Results:  Asthma control was unsatisfactory (44.27% of uncontrolled patients), as well as HRQoL. Controlled patients controlled showed significantly lower scores in all the RHINASTHMA domains compared to uncontrolled. Irrespective of their level of control, patients with rhinitis symptoms showed worse HRQoL in Upper Airways (UA) ( P  < 0.0001), Lower Airways (LA) ( P  < 0.001), and Global Summary (GS) ( P  < 0.0001). In patients with symptomatic rhinitis, RHINASTHMA were lower in controlled asthma patients (UA P  = 0.002; LA P  < 0.0001; RAI P  < 0.01; GS P  < 0.0001). Asthma control was associated with lower T5SS score ( P  = 0.034).
Conclusion:  Asthma control in real life is unsatisfactory. Rhinitis and asthma influence each other in terms of control and HRQoL. The control of rhinitis in asthma patients can lead to an optimization of HRQoL related to the upper airways, while this phenomenon is not so evident in asthma. These results suggest to strengthen the ARIA recommendation that asthma patients must be evaluated for rhinitis and vice versa.     

Omalizumab therapy: patients who achieve greatest benefit for their asthma experience greatest benefit for rhinitis

Background:  Asthma and rhinitis are considered components of a single IgE-mediated inflammatory disorder. However, despite being shown to often co-exist, they are typically treated as independent conditions. Omalizumab, an anti-IgE antibody, has proven effective in the treatment of both asthma and rhinitis.
Aims:  To examine whether a response to omalizumab in terms of asthma control predicts a higher likelihood of rhinitis response in patients with concomitant allergic asthma and rhinitis.
Methods:  This post hoc analysis was conducted on efficacy results from the SOLAR trial in which patients with moderate-to-severe asthma and rhinitis were randomized to receive omalizumab or placebo for 28 weeks. Patients were classified as asthma responders based on the physician's overall assessment (complete control or marked improvement in a five-level evaluation). Rhinitis responders were identified using the Rhinitis Quality of Life Questionnaire (RQLQ) questionnaire (≥ 1.0 point improvement in overall score).
Results:  Data were available for 207 omalizumab-treated patients and 192 placebo patients. According to the physicians overall assessment, 123 (59.4%) of omalizumab-treated patients were asthma responders, with the likelihood of a rhinitis response significantly ( P   <  0.001) greater in these patients than in the placebo group. The odds ratio for rhinitis response in omalizumab-treated asthma responders vs nonresponders was 3.56 (95% CI: 1.94–6.54).
Conclusions:  A response in terms of asthma following omalizumab therapy is associated with a significantly increased probability of improvement in rhinitis.     

Impact of allergic rhinitis on asthma: effects on spirometric parameters

Background:  Close association exists between allergic rhinitis and asthma. Moreover, allergic rhinitis is a strong risk factor for the onset of asthma in adults. This study was aimed at evaluating a large group of patients with moderate-to-severe and persistent allergic rhinitis alone for investigating the presence of spirometric abnormalities and possible risk factors related to it.
Methods:  A total of 392 patients with persistent allergic rhinitis were prospectively and consecutively evaluated. Clinical examination, skin prick test and spirometry were performed in all patients.
Results:  There were 24 (6.1%) patients with forced vital capacity (FVC < 80%) of predicted, 50 (12.8%) with forced expiratory volume in the first second (FEV₁ < 80%) of predicted and 341 (87.0%) with forced expiratory flow at 25% and 75% of the pulmonary volume (FEF_25–75) < 80% of predicted. The logistic regression analysis evidenced that rhinitis duration (OR_Adj: 1.9/year) and sensitization to house dust mites (OR_Adj: 8.2) were significantly associated with impaired values of 2 or 3 spirometric parameters.
Conclusion:  This study highlights the close link between upper and lower airways and the role of some risk factors, such as duration and mites sensitization, as early prognostic markers of bronchial involvement in patients with moderate-to-severe and persistent allergic rhinitis alone.     

Monitoring adherence to beclomethasone in asthmatic children and adolescents through four different methods

Background:  Suboptimal adherence to inhaled steroids is a known problem in children and adolescents, even when medications are administered under parental supervision. This study aimed to verify the adherence rate to beclomethasone dipropionate (BDP) by four currently available methods.
Methods:  In this concurrent cohort study, 102 randomly selected asthmatic children and adolescents aged 3–14 years were followed for 12 months. Adherence rate was assessed every 2 months by self and/or parent report, pharmacy dispensing data, electronic device (Doser^®; Meditrack Products, Hudson, MA, USA) monitor, and canister weight.
Results:  Mean adherence rates to BDP by self and/or parent report, pharmacy records, Doser, and canister weight were 97.9% (95% CI 88.0–98.6), 70.0% (95% CI 67.6–72.4), 51.5% (95% CI 48.3–54.6), and 46.3% (95% CI 44.1–48.4), respectively. Agreement analysis between (Doser) and canister weight revealed a weighted kappa equal to 0.76 (95% CI 0.65–0.87).
Conclusions:  Adherence was a dynamic event and rates decreased progressively for all methods over the 12-month follow-up. Canister weight and electronic monitoring measures were more accurate than self/parent reports and pharmacy records. Rates obtained by these two methods were very close and statistical analysis also showed a substantial agreement between them. As measurements by canister weight are less costly compared with currently available electronic devices, it should be considered as an alternative method to assess adherence in both clinical research and practice.     

Smoke exposure interacts with ADAM33 polymorphisms in the development of lung function and hyperresponsiveness

Introduction:  ADAM33 is the first identified asthma gene by positional cloning, especially asthma combined with bronchial hyperresponsiveness (BHR). Moreover, ADAM33 is associated with early-life lung function and decline of forced expiratory volume in 1 s (FEV₁) in the general population. In utero and postnatal cigarette smoke exposure (CSE) are associated with reduced lung function, and development of BHR and asthma. We hypothesized that this may occur via interaction with ADAM33.
Aim:  To replicate the role of ADAM33 in childhood lung function and development of BHR and asthma. Furthermore, we investigated gene–environment interaction of ADAM33 with in utero and postnatal CSE in the Dutch PIAMA cohort.
Methods:  Six ADAM33 single-nucleotide polymorphisms (SNPs) were genotyped. Rint was measured at age 4 and 8 years, FEV₁ and BHR at age 8 years; asthma was based on questionnaire data at age 8.
Results:  In the total cohort, the rs511898 A, rs528557 C, and rs2280090 A alleles increased the risk to develop asthma (+BHR). There existed interaction between in utero but not postnatal CSE and the rs528557 and rs3918396 SNPs with respect to development of BHR, the rs3918396 SNP with Rint at age 8 and the rs528557 SNP with FEV₁% predicted.
Conclusions:  We confirm associations between ADAM33 and the development of asthma (+BHR). This is the first study suggesting that interaction of in utero CSE with ADAM33 results in reduced lung function and the development of BHR, which needs further confirmation.     

Indacaterol provides sustained 24 h bronchodilation on once-daily dosing in asthma: a 7-day dose-ranging study

Background:  Indacaterol is a novel, once-daily β₂-agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. Studies were required to determine optimal dose(s) for continuing investigation.
Objective:  A dose-ranging study was undertaken to evaluate efficacy and safety of indacaterol.
Methods:  A total of 436 patients with persistent asthma receiving inhaled corticosteroids were randomized to 7 days treatment with once-daily indacaterol 50, 100, 200, or 400 μg via multi-dose dry-powder inhaler (MDDPI; Certihaler^™), indacaterol 400 μg via single-dose dry-powder inhaler (SDDPI), or placebo. Serial 24-h spirometry was performed on days 1 and 7. Vital signs, laboratory evaluations, and adverse events were monitored.
Results:  All doses of indacaterol increased the mean time-standardized area under the curve of forced expiratory volume in 1 s (FEV₁) from 22 to 24 h postdose ( P  ≤ 0.001 vs placebo) on days 1 and 7, with clinically relevant treatment-placebo differences of 240, 260, 350, 300, and 380 ml on day 1 and 230, 220, 320, 250, and 270 ml on day 7 for indacaterol 50, 100, 200, and 400 μg via MDDPI and 400 μg via SDDPI, respectively. All doses increased mean FEV₁ ( P  < 0.05 vs placebo) from 5 min to 24 h postdose on days 1 and 7. All doses were well tolerated. Most adverse events were mild-to-moderate in severity: most frequently reported were respiratory, thoracic, and mediastinal disorders.
Conclusion:  Once-daily dosing with indacaterol provided sustained 24-h bronchodilation in patients with moderate-to-severe asthma, with a satisfactory overall safety profile. Indacaterol 200 μg appears the optimum dose, offering the best efficacy/safety balance.     

Add-on omalizumab improves day-to-day symptoms in inadequately controlled severe persistent allergic asthma

Background:  Omalizumab is efficacious in the treatment of moderate-to-severe and severe persistent allergic (immunoglobulin E-mediated) asthma, reducing exacerbations, emergency visits and improving quality of life (QoL). However, as exacerbations are relatively infrequent, assessment of efficacy on day-to-day symptoms is warranted.
Aims:  To investigate the effect of add-on omalizumab on day-to-day symptoms, and how they correlate with QoL in severe persistent asthma.
Methods:  The correlation between asthma symptom scores and QoL [Asthma Quality of Life Questionnaire (AQLQ)] was assessed. Symptom-free days (total symptom score = 0) and symptom-controlled days (definition 1: total symptom score ≤1; and definition 2: morning peak expiratory flow ≥90% of baseline, daytime asthma score ≤1 and night-time asthma score = 0) were compared between the omalizumab-treated group, omalizumab responders and placebo.
Results:  Four hundred and nineteen patients (omalizumab, n  = 209; placebo, n  = 210) were included in the efficacy analyses, and 61% (118/195) of patients with response data were classified as responders. Total symptom score strongly correlated with AQLQ overall and symptom scores and individual domains. AQLQ overall score correlated well with symptom scores. Responders had significantly more symptom-free days than the omalizumab-treated and placebo groups (45.8%, 37.2% and 22.6% respectively), and more symptom-controlled days (definition 1: 56.1%, 47.9% and 35.3%, respectively, and definition 2: 50.8%, 43.9% and 28.0%, respectively).
Conclusions:  In patients with inadequately controlled severe persistent asthma, day-to-day symptoms correlate well with QoL. Add-on omalizumab significantly improves day-to-day symptoms compared with placebo. Further improvement in responders confirms the physician's assessment as a response measure.     

A breath for health: an exploratory study in severe asthma patients in Turkey

Background:  Severe asthma puts enormous burden on patients. To evaluate asthma-related restrictions on patients' daily lives along with their expectations about future asthma care.
Methods:  A structured questionnaire was administered to severe asthma patients at 25 centers across Turkey. The patients were divided into; uncontrolled ( n : 274) and controlled asthma ( n : 177) according to the existence of symptoms despite the GINA step 4 or 5 treatment.
Results:  A total of 451 patients (F/M: 337/114, mean age: 47.6 ± 13.2 years) were included; 93% were nonsmokers and 51.2% were atopic. Chronic rhino-sinusitis, ASA/NSAID sensitivity, and osteoporosis were significantly higher in uncontrolled patients. Nearly 70% of the uncontrolled asthmatics defined asthma as disturbing with significant restrictions in daily life. The most important role for medication was symptom relief. One inhaler or one tablet a month was the most preferred form of drug usage. In addition, 30.6% of the patients had tried alternative treatment with herbal remedies. Although patients were willing to become members of an asthma association, they expected the Turkish government to provide special asthma clinics and fund research into new treatments. Controlled patients achieved or were close to achieving asthma control goals. Uncontrolled patients seemed to be more pessimistic in this respect, but they reserved significant levels of hope for the future. Two-thirds of all the patients thought that they would receive better treatment in the next 5 years.
Conclusions:  In this study group, severe asthma patients face significant limitations in their daily lives, but they are optimistic about better asthma control and treatment options in the future.     

Clinical efficacy of budesonide Turbuhaler® compared with that of beclomethasone dipropionate pMDI with volumatic spacer

A total of 102 patients had their asthma treatment with beclomethasone dipropionate (BDP) optimized in order to achieve the best possible control of symptoms. Thereafter, the BDP doses were gradually reduced over a 2-year period (1988–90) to the lowest possible without deterioration of their asthmatic condition. In the beginning of 1990, treatment was changed in 76 patients (group A) to the nearest possible dose of budesonide delivered via Turbuhaler® Twenty-six randomly selected patients (25% of the study population; group B) continued treatment with BDP. In both groups, dose reductions were tried during 1990–2 every third month as long as the patients remained symptom-free and without significant decreases in FEV₁ or PEF. In group A, the maintenance dose could be reduced from 1003.9 ± 325.4 μg BDP (mean ± SD) to 602.9 ± 454.4 μg budesonide Turbuhaler ( P <0.001). In group B, no significant dose reduction was possible; the mean dose was ± SD 1067.3 ± 36.6 μg in 1990, and 1019.2 ± 324.7 μg in 1992. The results indicate that, in efficacy, 0.6 mg budesonide Turbuhaler corresponds to approximately 1.0 mg BDP with volumatic spacer. This difference is probably due to an improved pulmonary delivery of budesonide with Turbuhaler.     

Childhood Asthma Control Test and airway inflammation evaluation in asthmatic children

Background:  The Childhood Asthma Control Test (C-ACT) has been proposed as a tool in assessing the level of disease control in asthmatic children. To evaluate the position of C-ACT in the clinical management of asthmatic children, in relationship to the level of airway inflammation as assessed by fractional exhaled nitric oxide (FeNO) and with lung function.
Methods:  A total of 200 asthmatic children were included in the study: 47 children with newly diagnosed asthma ('New') and without any regular controller therapy; and 153 children with previously diagnosed asthma, treated according to GINA guidelines, and evaluated during a scheduled follow-up visit ('Follow-up'). Childhood Asthma Control Test, FeNO and lung function [forced expiratory volume 1 (FEV1) and forced vital capacity (FVC)] were evaluated.
Results:  In New vs Follow-up participants, C-ACT score ( P  <   0.001), FVC ( P  <   0.005) and FEV1 ( P  <   0.05) were significantly lower, and FeNO ( P  =   0.011) were significantly higher. In New, but not in Follow-up participants, significant correlations were observed between C-ACT score and FeNO ( r  = −0.51; P  <   0.001), FEV1 ( r  =   0.34; P  =   0.022) and FEV1/FVC ( r  =   0.32; P  =   0.03). This lack of correlation in Follow-up visits seemed attributable to dissociation between inadequately controlled asthma by C-ACT ratings with normalization of other measures such as FeNO levels.
Conclusions:  This study confirms and expands the concept that C-ACT is complementary to, but not a substitute for, other markers of disease control in asthmatic children, especially in the context of follow-up visits.     

Comparison between sodium cromoglycate (MDI: metered-dose inhaler) and beclomethasone dipropionate (MDI) in treatment of adult patients with mild to moderate bronchial asthma A double-blind, double-dummy randomized, parallel-group study

This study compared the efficacy and tolerability of sodium cromoglycate (SC) and beclomethasone dipropionate (BDP) in adult patients with bronchial asthma inadequately treated with bronchodilators alone. The study was a double-blind, randomized, double-dummy, parallel-group study. Patients with mild to moderate symptomatic asthma, inadequately treated with bronchodilators only, were, after a 2–week run-in (base-line) period, randomized to 8 weeks of treatment with either SC 10 mg four times daily or BDP 100 μg four times daily. Salbutamol metered-dose inhaler was given as relief medication. A total of 37 patients were randomized for treatment, 19 patients in the SC group and 18 patients in the BD group. Efficacy and safety were determined by daily record card data: morning and evening peak-expiratory-flow rates (PEER), daytime and nighttime asthma symptom scores, and rescue salbutamol use. At clinic visits, FEV₁ and FVC were measured, as were the physician's and the patient's assessment of the medication at the end of the study. The safety and tolerability of the trial medication were assessed by monitoring adverse events throughout the study. A clinically and statistically significant improvement of the asthma in FEV₁, symptom scores, rescue medication, and global opinion of efficacy was observed, and both groups provided equivalent efficacy. The morning PEFR as well as the evening PEFR for both groups improved, but was statistically significant only for the BDP group (M-PEFR). Both drugs were well tolerated with only a few minor adverse events. This trial shows that SC and BDP are equally effective anti-inflammatory treatments for mild to moderate bronchial asthma in adults.     

Stability of asthma control with regular treatment: an analysis of the Gaining Optimal Asthma controL (GOAL) study

Background:  Uncontrolled asthma is characterized by variability. Current asthma guidelines recommend focussing on the achievement and maintenance of control but few studies have examined in detail, using composite measures of control, the stability and potential duration of control once achieved. In this post-hoc analysis of the results of the Gaining Optimal Asthma controL (GOAL) study, we examine the association between the level of asthma control achieved during the step-up phase of the study and the stability of control experienced during the maintenance phase.
Methods:  GOAL was a 1-year, randomized, stratified, double-blind study of 3421 patients with uncontrolled asthma, which compared salmeterol/fluticasone propionate combination with fluticasone propionate in achieving two composite, guideline-based measures of control: totally controlled and well-controlled asthma. We analysed the proportion and duration of time spent in control, the effect of treatment on asthma stability, and the impact of asthma control stability on unscheduled use of healthcare resources.
Results:  In patients achieving well-controlled or totally controlled asthma, at least well-controlled asthma was maintained for a median of almost 3 and 6 months, and for more than 85% and 95% of weeks of follow-up, respectively. A high level of stability was confirmed in a Markov analysis investigating transitional probability of change in control status. Variability in control was associated with increased probability of an unscheduled healthcare resource use (odds ratio: 1.06, P  < 0.001).
Conclusions:  Most patients achieving guideline-defined control can maintain at least a similar level of control with regular, stable dosing, with little likelihood of losing control.     

Masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid-dependent asthmatics

Background:  Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma.
Objectives:  The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints.
Methods:  A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management.
Results:  At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of ­78% and ­57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 ( P  < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema.
Conclusions:  Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma (ClinicalTrials.gov Identifier: NCT00842270).     

Under-report and underdiagnosis of chronic respiratory diseases in an African country

Background:  Chronic respiratory diseases (CRD) are greatly underestimated. The aim of this study was to assess the burden associated with reported CRD and chronic obstructive pulmonary disease, as defined on the basis of various standardized criteria, by estimating their point prevalence in a sample of individuals attending the Primary Health Care (PHC) level and Emergency Room (ER) Departments in Cape Verde (CV) archipelago. The second aim of the study was to identify factors related to airways obstruction and reported CRD in this population.
Methods:  A cross-sectional study was carried out in CV during 2 weeks. Outpatients aged more than 20 years seeking care at PHC level and ER answered a standardized questionnaire and were subjected to spirometry, independently of their complaint. Two criteria for airways obstruction were taken into account: forced expiratory volume (FEV₁) <80% of the predicted value and FEV₁/forced vital capacity (FVC) ratio <0.70.
Results:  A total of 274 individuals with a satisfactory spirometry were included. 22% of the individuals had a FEV₁ < 80%. Individuals older than 46 years had a higher risk of having airways obstruction. Asthma diagnosis (11%) had a clear association with airways obstruction. Smoking was a risk factor for a lower FEV₁. Working in a dust place and cooking using an open fire were both related to chronic bronchitis and asthma diagnosis.
Conclusion:  Under-report and underdiagnosis of chronic respiratory conditions seem to be a reality in CV just as in other parts of the world. To improve diagnosis, our results reinforce the need of performing a spirometry.     

Neutrophilic airway inflammation is a main feature of induced sputum in nonatopic asthmatic children

Background:  Asthma phenotypes are well described among children. However, there are few studies comparing airway inflammation in different clinical presentations of pediatric asthma. We tested the hypothesis that nonatopic asthma is associated with a predominant noneosinophilic inflammation in the airways, as assessed by induced sputum. The objective of this study was to evaluate the cytological characteristics of induced sputum (IS) in atopic (AA), nonatopic asthmatics (NAA) and nonatopic nonasthmatic children (NANA).
Methods:  Of 90 selected children, 77 met eligibility criteria for performing IS and were classified as: AA, n  = 28, NAA, n  = 29 and NANA, n  = 19. Subjects answered to a set of ISAAC-based questions and were skin-tested for common aeroallergens. A defined series of exclusion criteria was applied.
Results:  Induced sputum was obtained from 54 (70.1%) subjects (21 AA, 20 NAA and 13 NANA). Demographic data and mean FEV₁ were similar in the three groups. The proportion of eosinophils [median, inter quartile range (IQR)] was significantly higher in the sputum of AA [(6.0.)12)] compared with NAAs [0 (2)] and NANAs [0 (1)], P  < 0.001. The proportion of children with sputum eosinophilia (eos > 3%) was also significantly higher in AA (71.4%) when compared with NAA (28.6%); none of the NANA had sputum eosinophilia. Nonatopic asthmatic children had significantly higher proportions and absolute number of neutrophils than AA and controls.
Conclusions:  The results suggest that nonatopic children present IS with a cell pattern that is predominantly neutrophilic while eosinophilia is the hallmark of airway inflammation in the majority of atopic wheezing children not treated with inhaled steroids.     

Fitness, daily activity and body composition in children with newly diagnosed, untreated asthma

Background:  Information about how the asthma disease affects the life style and health in children is sparse.
Aim:  To measure fitness, daily physical activity and body composition in children with newly diagnosed, untreated asthma and healthy controls, and to assess the association between the level of asthma control and these parameters.
Methods:  Daily physical activity measured using accelerometry, cardiovascular fitness and body composition (per cent fat, per cent lean tissue and bone mineral density) were measured in 57 children with newly diagnosed, untreated asthma and in 157 healthy age- and sex-matched controls. The level of asthma control was assessed by measurements of a variety of asthma outcomes.
Results:  Children with asthma were less fit (35.1 vs 39.3 ml O₂/min/kg) ( P  < 0.001), had a higher body per cent fat (22.8 vs 19.5%) ( P  < 0.01) and a higher frequency of overweight (24.6 vs 14.2%) ( P  < 0.05) than healthy controls. Per cent body fat correlated negativly to overall daily activity ( P  < 0.001) and to time spent in high or vigorous activity ( P  < 0.001). Fitness corrrelated positively to time spent in high and vigorous activity ( P  < 0.001). Within the asthma group, the level of asthma control, fitness and the time spent in vigorous activity correlated positively ( P  < 0.02).
Conclusion:  Children with untreated asthma are less fit and have a higher body per cent fat and frequency of obesity than their healthy peers. Uncontrolled asthma is associated with a reduced fitness and daytime spent in intensive activity. Overweight children are physically less active than normal weight children.     

Dose–response relationship for risk of non-vertebral fracture with inhaled corticosteroids

Objective To determine the strength of association between the dose of inhaled corticosteroids (ICS) and risk of non-vertebral fracture in adults.
Methods A systematic review and meta-analysis of case–control studies of non-vertebral fractures in adults, in which at least two doses of ICS were reported as the dose of beclomethasone dipropionate (BDP) or equivalent.
Results Five case–control studies were identified, with a total of 43 783 cases and 259 936 controls. There was an association between the risk of non-vertebral fracture and increasing dose of BDP. The random-effects odds ratio of relative risk for a non-vertebral fracture was 1.12 (95% confidence interval 1.00–1.26) per 1000 μg increase in the daily dose of BDP or equivalent.
Conclusion In older adults, the relative risk of non-vertebral fractures increases by about 12% for each 1000 μg/day increase in the dose of BDP or equivalent. The magnitude of this risk was considerably less than other common risk factors for fracture in the older adult.     

Lack of control of severe asthma is associated with co-existence of moderate-to-severe rhinitis

Background:  Retrospective studies provide evidence that rhinitis is associated with more severe asthma. The aim of this study was to evaluate prospectively whether rhinitis is a predictor of increased asthma severity.
Methods:  Five hundred and fifty-seven patients with severe asthma were enrolled. During 1 year of follow-up, each patient was evaluated every 3 months with a record of emergency room visits and supply of topical corticosteroids for asthma and rhinitis. In the 1 year of follow-up visit, the patients were checked for rhinitis diagnosis, severity and answered questionnaires for asthma symptoms and quality of life.
Results:  Eighty-two (15%) patients had no rhinitis, 299 (54%) had mild rhinitis and 176 (31%) moderate/severe rhinitis. In logistic regression models, moderate/severe rhinitis was a predictor for any emergency room visit in the follow-up period [3.83 (2.00–7.35)], for the presence of uncontrolled asthma after 1 year of follow-up [12.68 (1.73–92.85)], for <10% improvement of the airway obstruction [2.94 (1.48–5.85)] and <50% reduction in the number of emergency room visits [2.90 (1.02–8.26)] in the year of follow-up. It was also associated with a smaller chance of more than 90% reduction in the number of emergency room visits in the year of follow-up [0.27 (0.12–0.60)]. In a multivariate linear regression model, severity of rhinitis was positively correlated with a score of asthma severity and inversely correlated to an index of quality of life.
Conclusions:  In a population with severe asthma, moderate/severe rhinitis is a strong predictor for greater severity of asthma.