Inhaled Steroid Therapy Research Articles

Sex differences in use of inhalants by elderly patients with asthma.

BackgroundThe number of elderly patients with asthma has been increasing in Japan. Treatment for these patients should be provided based on the condition of individual patients. This study was performed to clarify the relationship between inhalation procedure and sex difference in elderly patients with asthma.MethodsThe inhalation procedure was examined in 155 elderly patients with asthma (male: n=66, average age ± standard deviation: 75.5±5.65 years old; female: n=89, average age ± standard deviation: 78.7±6.87 years old) during a medical examination.ResultsFor the three items that were common to all devices, the percentages of the 155 patients who could/could not perform the actions were examined by separate Fisher’s exact tests for males and females. A statistically significant difference (P=0.007) was observed for “breath holding”, and more females than males were not able to hold their breath. Although no significant difference was seen in the “accurate number of times of inhalation”, females tended to not be able to inhale accurately compared to males (P=0.072).ConclusionOur results suggest that elderly female patients with asthma have less understanding of inhaled steroid therapy, compared to elderly male patients. Therefore, it is particularly important to confirm that the correct inhalation procedure is used by elderly female patients with asthma.

Inappropriate prescribing of combination inhalers in Northern Ireland: retrospective cross-sectional cohort study of prescribing practice in primary care

Background:Asthma management guidelines advocate a stepwise approach to asthma therapy, including the addition of a long-acting bronchodilator to inhaled steroid therapy at step 3. This is almost exclusively prescribed as inhaled combination therapy.Aims:To examine whether asthma prescribing practice for inhaled combination therapy (inhaled corticosteroid/long-acting β2-agonist (ICS/LABA)) in primary care in Northern Ireland is in line with national asthma management guidelines.Methods:Using data from the Northern Ireland Enhanced Prescribing Database, we examined initiation of ICS/LABA in subjects aged 5–35 years in 2010.Results:A total of 2,640 subjects (67%) had no inhaled corticosteroid monotherapy (ICS) in the study year or six months of the preceding year (lead-in period) and, extending this to a 12-month lead-in period, 52% had no prior ICS. 41% of first prescriptions for ICS/LABA were dispensed in January to March. Prior to ICS/LABA prescription, in the previous six months only 17% had a short-acting β2-agonist (SABA) dispensed, 5% received oral steroids, and 17% received an antibiotic.Conclusions:ICS/LABA therapy was initiated in the majority of young subjects with asthma without prior inhaled steroid therapy. Most prescriptions were initiated in the January to March period. However, the prescribing of ICS/LABA did not appear to be driven by asthma symptoms (17% received SABA in the previous 6 months) or severe asthma exacerbation (only 5% received oral steroids). Significant reductions in ICS/LABA, with associated cost savings, would occur if the asthma prescribing guidelines were followed in primary care.

Epidemiology characteristics of bronchial asthma in children aged 0-14 years old in Tianjin urban

Objective To explore the prevalence and correlative factors of childhood asthma in urban areas in Tianjin, and to assess the influence of asthma on patients' social life and their families. Methods A cluster random survey of asthma was conducted among the children in Tianjin.The respondents were 0-14 years old children (birth on Jul.1, 1995 to Jun.30, 2010) in Tianjin. Results Totally 12 748 subjects were investigated by means of questionnaires to the parents, among whom 355 children were diagnosed as asthma(294 as typical asthma, 61 as cough variant asthma), and the male/female ratio was 1.56︰1.00.The total prevalence rate of asthma in Tianjin urban children was 2.78%(355/12 748 cases), while the 2 years prevalence rate was 2.14%(273/12 748 cases), and they were significantly higher than 10 years ago, and 48.45%(172/355 cases) of the children had their onset less than 3 years old.Asthmatic attack occurred more often during December to February, and respiratory tract infection was main inducement, and most frequently precursory symptoms were runny nose and sneezing, while the symptoms during attack were usually cough and wheezing, and 57.46%(204/355 cases) of the patients with asthma had history of allergic rhinitis.For 96.34%(263/273 cases) of the patients, their family members' work was affected because of their asthma attacks, and 252 patients(70.99%, 252/355 cases) had used inhaler corticosteroid, and 57.18%(203/355 cases) of the patients had used antibiotics. Conclusions There has been a significantly increasing trend of asthma prevalence during the 10 years in all age group.From the data of present survey it was inferred that there had been certain improvement, though it was not ideal in the accuracy of diagnosis and in the practice of steroid inhalation therapy by the pediatricians in Tianjin. Key words: Asthma; Prevalence; Child

A Comparison of Characteristics and Outcomes in Severe Human Metapneumovirus and Respiratory Syncytial Virus Infections in Children Treated in an Intensive Care Unit

Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are among the leading causes of respiratory tract infections requiring admission to the pediatric intensive care unit (PICU). We evaluated the risk factors, clinical courses and outcomes of severe HMPV disease relative to severe RSV in children admitted to the PICU. Retrospective chart review of children ≤18 years old admitted to a tertiary PICU between October 2008 through July 2010 with acute respiratory tract infection and positive direct antigen stain or polymerase chain reaction for RSV or HMPV. One hundred thirty-three patients met inclusion criteria: 107 (80.5%) with RSV and 26 (19.5%) with HMPV. HMPV-infected patients were older than RSV children (3.4 vs. 1.5 years, P = 0.002) and more likely to have congenital heart disease (34.6% vs. 10.3%, P = 0.002). Although HMPV children required longer duration of mechanical ventilation (11 vs. 7 days, P = 0.01), there were no other differences in hospital course. HMPV patients were more likely to be discharged receiving inhaled steroids (53.8% vs. 30.8%, P = 0.03), but there were no differences in other outcome assessments. Children admitted to the PICU with HMPV are significantly older and more likely to have congenital heart disease than those with RSV. The course of illness was similar between the 2 groups, but HMPV-infected children were more likely to be discharged with inhaled steroid therapy.

Pharmocogenetic predictors of inhaled budesonide response in asthma

There is considerable interindividual variability in response to inhaled corticosteroids for treatment of asthma. Although there is evidence that some of this variability is mediated by genetic factors, as of yet, there are no clear predictors of clinical response to inhaled steroids, particularly in relation to drug metabolism and transport processes. The goal of our study was to better understand the contribution of pharmacogenetic differences for patients with asthma whose treatment regimen includes budesonide, a widely prescribed inhaled steroid, known to be metabolized by CYP3A4 and transported by MDR1(ABCB1). We have enrolled 50 patients with confirmed asthma who were on a stable dose of inhaled budesonide alone (Pulmicort) or in combination with a long acting beta‐agonist formoterol (Symbicort). We will genotype for known polymorphisms in CYP3A4 (*22) and CYP3A5*3, as well as commonly occurring polymorphisms in MDR1. Importantly, we will also measure beta‐hydroxycholesterol/cholesterol ratio as an in vivo probe of CYP3A activity and measure budesonide plasma levels using highly sensitive liquid chromatography‐tandem mass spectrometry. Pharmacogenetic markers will be correlated with drug levels, clinical efficacy, pulmonary function, and exhaled nitric oxide as a marker of airway inflammation. Our findings will lead to better pharmacogenetic predictors of inhaled steroid therapy efficacy. Supported by Program of Experimental Medicine, Department of Medicine, Western University.

Ultrasound velocity through the tibia is not affected by prolonged inhaled steroid therapy in children

To evaluate in a prospective, cross-sectional cohort study the impact of inhaled corticosteroids (ICS) on bone speed of sound (SOS) in asthmatic children. Children with mild-to-moderate asthma from a pulmonary clinic were assessed over a 2-month period. We recorded clinical and demographic data related to asthma severity, its treatment, participation in sports and dairy intake. Tibial SOS was measured using the Sunlight Omnisense 7000S quantitative ultrasound bone sonometer. Eighty-five mild-to-moderate asthmatic children were studied. Age range was 1.4-17 years (71.7% boys). Average disease duration was approximately 5 years, and the average cumulative duration of ICS therapy was approximately 1.5 years. Average SOS Z-score was slightly negative and varied between -3.5 and +1.9 SD. In univariate analysis, SOS Z-score was negatively correlated with asthma duration (R(2) = 5.7%, p = 0.028) and ICS duration (R(2) = 4.9%, p = 0.042). In backward stepwise multiple regression, where SOS Z-score was the dependent variable, the only variables that remained significant in the final analysis were gender (p = 0.015), asthma duration (p = 0.003) and BMI (p = 0.048) (R(2) for the model 17.52% p = 0.01). Prolonged inhaled steroid therapy appears to have no deleterious effect upon SOS in children with mild-to-moderate persistent asthma.

671 Exhaled Nitric Oxide and Pulmonary Function in Children with Allergic Asthma

Background and AimsNitric oxide (NO) is a marker of eosinophilic inflammation in airways and can be measured in exhaled air. Fractional exhaled nitric oxide (FeNO) is elevated in allergic asthma....

Overweight is Associated with Airflow Obstruction and Poor Disease Control but Not with Exhaled Nitric Oxide Change in an Asthmatic Population

Background: The role of an elevated body mass index (BMI) in asthma remains controversial. Objectives: To investigate the relationship between overweight (BMI >25 and ≤30), lung function, disease control, and airway inflammation in an asthmatic population. Methods: We consecutively studied 348 patients (age 43 ± 16 years; 211 females). In all patients, BMI, spirometry, the Asthma Control Test (ACT), and fractional exhaled nitric oxide (FeNO; ppb) were measured. Results: One hundred forty-five patients were overweight and, as compared to those with normal BMI, had lower values of FVC, FEV₁, and FEV₁/FVC and of FEF_25–75 even when normalized for FVC (p < 0.05 for each comparison). The ratio between the number of patients with well-controlled asthma (ACT ≥20) and that of patients with poorly controlled asthma (ACT < 20) was significantly lower in overweight patients (1.07 vs. 1.84; χ² = 6.030, p < 0.01). In overweight patients, the odds ratio of uncontrolled asthma expressed by logistic regression analysis was 1.632 (95% CI = 1.043–2.553), independently of gender, atopy, smoking habit, and inhaled steroid therapy. No difference was observed in FeNO values between overweight and normal weight patients (27.7 ± 2.3 vs. 27.9 ± 2.2 ppb). Conclusions: Our results show that, in an asthmatic population, overweight is associated with airflow obstruction and poor disease control but not with FeNO change. The findings of the present study support the view that other factors besides airway inflammation alone may explain the relationship between asthma and an elevated BMI.

Budesonide Therapy in Preterm Infants to Prevent Bronchopulmonary Dysplasia

Severe bronchopulmonary dysplasia (BPD) is common disease, especially for the tiniest infants with gestational age &amp;lt;27 weeks whose mothers did not receive adequate antenatal steroid prophylaxis. Systemic corticosteroids have been demonstrated to be effective in the prevention of BPD, but their adverse effects prevent routine use. The results of inhaled steroid therapy in intubated premature infants are disappointing. In a pilot study, infants in the treatment group who received early intratracheal instillation of budesonide by using surfactant as a vehicle required significantly less ventilator support during the first 2 weeks than infants in the control group. The combined outcome of deaths or BPD was significantly lower in the treatment group than in the control group. No clinically significant adverse effects from the treatment were observed during the study. The results are encouraging, and a large sample multicenter trial is warranted.

Inhaled corticosteroids for stable chronic obstructive pulmonary disease.

The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much controversy. Major international guidelines recommend selective use of ICS. Recently published meta-analyses have reported conflicting findings on the effects of inhaled steroid therapy in COPD. To determine the efficacy and safety of inhaled corticosteroids in stable patients with COPD, in terms of objective and subjective outcomes. A pre-defined search strategy was used to search the Cochrane Airways Group Specialised Register for relevant literature. Searches are current as of July 2011. We included randomised trials comparing any dose of any type of inhaled steroid with a placebo control in patients with COPD. Acute bronchodilator reversibility to short-term beta(2)-agonists and bronchial hyper-responsiveness were not exclusion criteria. The a priori primary outcome was change in lung function. We also analysed data on mortality, exacerbations, quality of life and symptoms, rescue bronchodilator use, exercise capacity, biomarkers and safety. Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials. Fifty-five primary studies with 16,154 participants met the inclusion criteria. Long-term use of ICS (more than six months) did not consistently reduce the rate of decline in forced expiratory volume in one second (FEV(1)) in COPD patients (generic inverse variance analysis: mean difference (MD) 5.80 mL/year with ICS over placebo, 95% confidence interval (CI) -0.28 to 11.88, 2333 participants; pooled means analysis: 6.88 mL/year, 95% CI 1.80 to 11.96, 4823 participants), although one major trial demonstrated a statistically significant difference. There was no statistically significant effect on mortality in COPD patients (odds ratio (OR) 0.98, 95% CI 0.83 to 1.16, 8390 participants). Long-term use of ICS reduced the mean rate of exacerbations in those studies where pooling of data was possible (generic inverse variance analysis: MD -0.26 exacerbations per patient per year, 95% CI -0.37 to -0.14, 2586 participants; pooled means analysis: MD -0.19 exacerbations per patient per year, 95% CI -0.30 to -0.08, 2253 participants). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (MD -1.22 units/year, 95% CI -1.83 to -0.60, 2507 participants). Response to ICS was not predicted by oral steroid response, bronchodilator reversibility or bronchial hyper-responsiveness in COPD patients. There was an increased risk of oropharyngeal candidiasis (OR 2.65, 95% CI 2.03 to 3.46, 5586 participants) and hoarseness. In the long-term studies, the rate of pneumonia was increased in the ICS group compared to placebo, in studies that reported pneumonia as an adverse event (OR 1.56, 95% CI 1.30 to 1.86, 6235 participants). The long-term studies that measured bone effects generally showed no major effect on fractures and bone mineral density over three years. Patients and clinicians should balance the potential benefits of inhaled steroids in COPD (reduced rate of exacerbations, reduced rate of decline in quality of life and possibly reduced rate of decline in FEV(1)) against the potential side effects (oropharyngeal candidiasis and hoarseness, and risk of pneumonia).

Advances in the clinical applications of exhaled nitric oxide measurements

This article focuses on recent data which highlight the clinical settings in which exhaled nitric oxide (FENO) is potentially helpful, or not, as a clinical tool. It is becoming clearer that, selectively applied, FENO measurements can provide reliable clinical guidance, particularly when values are low. Such values are associated with high negative predictive values (>90%). Increased FENO levels are associated with much more modest positive predictive values (75%–85%) and these are less reliable. These general principles apply when diagnosing steroid responsiveness in relation to asthma, chronic cough, and COPD. Although randomised trials do not support routine use of exhaled NO measurements in uncomplicated bronchial asthma, there is evidence that in patients with difficult asthma, or asthma associated with pregnancy, FENO enhances overall management, and the decision to commence or increase inhaled steroid therapy (yes/no) may be made more accurately. Exhaled NO is potentially relevant in the assessment of occupational asthma (serial measurements) and also in diagnosing bronchiolitis obliterans in lung transplant patients.

Churg-Strauss syndrome related to montelukast

A young male with complaints of cough, dyspnea and hemoptysis was admitted. He was using fluticasone propionate and salmeterol for two years for his asthma. Leukotriene receptor antagonist was prescribed two weeks prior to his admission and no reduction of his inhaled steroid therapy was performed. Eosinophil count was detected as 1460/mm³ (15%) and immunoglobulin E level was 547 IU/mL. Thorax computerized tomography revealed patchy infiltration. Increased eosinophilic inflammation were detected in bronchoalveolar lavage fluid and transbronchial biopsy. He received prednisolone treatment for Churg-Strauss syndrome. Improvement was observed on three months follow up period. He has no complaint in his follow up.

Biophysical interaction between corticosteroids and natural surfactant preparation: implications for pulmonary drug delivery using surfactant a a carrier.

Intratracheal administration of corticosteroids using a natural pulmonary surfactant as a delivery vehicle has recently received significant attention in hopes of treating premature newborns with or at high risk for chronic lung disease. As a new practice, both the surfactant preparation used as the carrier and the corticosteroid delivered as the anti-inflammatory agent, and their mixing ratios, have not been standardized and optimized. Given the concern that corticosteroids delivered via a pulmonary surfactant may compromise its surface activity and thus worsen lung mechanics, the present study was carried out to characterize the biophysical interaction between a natural surfactant preparation, Infasurf, and two commonly used inhaled corticosteroids, budesonide and beclomethasone dipropionate (BDP). Based on surface activity measurements by the Langmuir balance and lateral film structure studied by atomic force microscopy, our findings suggest that when Infasurf is used as a carrier, a budesonide concentration less than 1 wt% of surfactant or a BDP concentration up to 10 wt % should not significantly affect the biophysical properties of Infasurf, thus being feasible for pulmonary delivery. Increasing corticosteroid concentration beyond this range leads to early collapse of the surfactant film due to increased film fluidization. Our study further suggests that different affinities to the surfactant films are responsible for the different behavior of budesonide and BDP. In addition to the translational value in treating chronic lung disease, this study may also have implications in inhaled steroid therapy to treat asthma.

S11 Inappropriate prescribing of combination inhalers in asthma in Northern Ireland (NI)

IntroductionBTS/SIGN asthma management guidelines recommend a stepwise approach to the use of anti-inflammatory therapy, including the addition of inhaled combination therapy (ICT) at Step 3. In NI, ICT accounts for...

Riesgo de neumonía en pacientes con enfermedad pulmonar obstructiva crónica estable en tratamiento con terapia inhalada con glucocorticoides

Background and objective Treatment with inhaled steroids is related to pneumonia and acute respiratory infection. The aim of this review is to quantify the effect inhaled steroids in pneumonia in stable chronic obstructive pulmonary disease (COPD) patients. Material and method We performed a systematic review of the systematic reviews that have studied inhaled corticosteroids in stable COPD patients. Results Inhaled steroid therapy in patients with clinically stable COPD causes an increase in the number of pneumonia. The NNTH of the analysed systematic reviews ranged from 12 subjects exposed to more than three years, to 80 subjects with one year follow up. Budesonide did not show this side effect. Conclusion It would be advisable to inform patients about the risk/benefit of these therapies.

P173 Management of sputum eosinophil-negative patients in a severe asthma clinic

Asthma is a heterogeneous disease that requires physicians to further phenotype their patients in order to offer carefully customised treatment. Among recent and rapidly evolving tools at clinicians' disposal are...

P180 Sputum eosinophil positivity to tailor steroid management of severe asthmatics

The use of sputum eosinophil count in asthma clinics is rapidly expanding as it has been reported as being a useful indicator of the worsening of asthma symptoms and that...

High dose steroid inhalation therapy using a large spacer: laboratory and clinical study on usefulness of the 4-puffs/inhalation method

We investigated whether or not the inhalation method of beclomethasone dipropionate (BDP) influences patient compliance and the clinical effects of therapy in chronic bronchial asthma, together with a basic study on the lung deposition of BDP using a twin Impinger when various numbers of puffs were discharged into three different spacers (Volumatic, InspirEase, Aerochamber). It was clearly shown that only the spacer, Volumatic maintained a high deposition rate of BDP in the lung model with a dose of 4-puffs/inhalation. Eighteen chronic asthmatic patients were studied. The patients inhaled BDP (800-1600 micrograms/day) by 1-puff/inhalation using a large spacer, Volumatic, for 12 weeks, and they then inhaled the same dose of BDP as given in the previous period by 4-puffs/inhalation using the spacer for 16 weeks. We compared the compliance of BDP, attack score, %PEFR and frequency of beta-agonist inhalation between these two periods. The compliance of BDP was markedly improved after changing from 1-puff/inhalation (92.8%) to 4-puffs/inhalation (99.8%). In the 4-puffs/inhalation period, attack score and %PEFR were significantly improved as compared to the 1-puff/inhalation period. The frequency of beta-agonist inhalation use in the 4-puffs/inhalation period was significantly lower than that in the 1-puff/inhalation period. These results indicate that when high dose steroid inhalation is given with a large spacer in chronic asthmatic patients, we should advice them of the appropriate inhalation method in order to obtain good compliance and clinical effects.

Hışıltılı Çocuklarda Lökotrien E4 ve Endotelin-1 Düzeyleri, Tedaviye Yanıt, Gastroösefageal Reflü ve Süt Çocuğu Astımı Gelişmesi ile Potansiyel İlişkileri

Objective: Wheezing is a common symptom among children and is proposed to be associated with inflammatory cell infiltration, cytokines production, and with some risk factors such as gastro esophageal reflux (GER). The aim of the present study was to investigate endotheline-1 (ET-1) and leukotriene-E4 (LTE-4) levels, their response to steroid and ?2-agonist therapy, and to establish if these parameters can be used as a diagnostic tool for infantile asthma and assess their relation with GER during acute attack of wheezy infants (WI). Material and Methods: Thirty WI and 12 healthy infants were enrolled in the present study. Serum IgE, ET-1, urine LTE-4 levels, and eosinophil percentage were measured prior to and 5 days after the treatment (systemic or inhaled steroid therapy and inhaled ?2-agonist) in children with WI. In addition, esophageal pH was monitored for 24 hours. Results: Serum IgE, ET-1, and urine LTE-4 levels were significantly higher in the patients compared to the controls before and five days after the treatment (p= 0.009; p= 0.039, p= 0.032; p= 0.014, p= 0.017, respectively). The serum IgE and urine LTE-4 levels prior to and 5 days after the treatment were higher in the patients with GER when compared to the controls (p= 0.021, p= 0.016 and p= 0.039). Moreover, the systemic or inhaled steroid therapy did not influence the serum ET-1 and urine LT-E4 levels. We found that the serum IgE and ET-1 levels on 5^th day of the treatment and LTE-4 levels at the beginning and 5th day of the treatment were notably different in patients with higher likelihood for developing infantile asthma when compared to the controls. Finally, increased serum IgE levels were present in patients with good response to inhaled ?2-agonist with regard to those with poor response to inhaled ?2-agonist (p= 0.031). Conclusion: The present study indicated that IgE, ET-1 and LTE-4 levels were related to airway inflammation in WI while LTE-4 and IgE levels were associated with GER. LTE-4 and IgE levels could be novel parameters for determining the risk factor for developing asthma in child with WI. Inhaled ?2-agonist therapy seemed to be beneficial only in patients with high serum IgE levels.

Matrix metalloproteinases‐7, ‐8, ‐9 and TIMP‐1 in the follow‐up of diisocyanate‐induced asthma

Diisocyanate-induced asthma (DIA) is known to be associated with poor prognosis. We wished to clarify if matrix metalloproteinases (MMP)-7, -8 or -9 or tissue inhibitor of matrix metalloproteinases (TIMP-1) are associated with the functional or inflammatory outcome in DIA patients. This is a longitudinal study where 17 patients with DIA diagnosed by a specific challenge test to diisocyanates were monitored. Exposure to diisocyanates was terminated seven (mean) months before the challenge test. The studies included spirometry, histamine challenge test and bronchoscopy. MMP-7, MMP-8, TIMP-1 [Enzyme-linked immunosorbent assay (ELISA)- and immunofluorometric assay-methods], MMP-9 (ELISA and zymography), interferon-gamma, tumour necrosis factor-alpha, interleukin-6, -8, -15, -17, CXCL-5/ENA-78, monocyte chemoattractant protein-1 and macrophage inhibitory factor (MIF) (ELISA) were assayed from bronchoalveolar lavage (BAL) fluid. Inhaled steroid therapy was initiated after the examinations, which were repeated at 6 months and at 3 years during the treatment. The results were compared with those of 15 healthy controls. Inhaled steroid medication increased BAL levels of MMP-9 and MMP-9/TIMP-1 and decreased MMP-7 and MMP-7/TIMP-1. The increase in MMP-9 levels was associated with a decline in the TH-2 type inflammation. Our data suggest that reduced TH-2 type inflammation in DIA after inhaled steroid medication is reflected as elevated MMP-9 and MMP-9/TIMP-1 levels in BAL. MIF may be the inducer of MMP-9. This might point to some protective role for MMP-9 in DIA.