High-dose Inhaled Corticosteroid Treatment Research Articles

Inhaled corticosteroid treatment and pneumonia in patients with chronic obstructive pulmonary disease – nationwide development from 1998 to 2018

ABSTRACT Background A decreasing use of inhaled corticosteroids (ICS) in patients with a hospital-registered diagnosis of chronic obstructive pulmonary disease (COPD) has recently been documented in Denmark. ICS treatment is not recommended in patients with high pneumonia risk, and we aimed to assess the development of ICS treatment in relation to pneumonia occurrence. Methods Annual nationwide register-based cross-sectional studies from 1998 to 2018 including all patients ≥40 years of age with a hospital-registered ICD-10 diagnosis of COPD on the 31st of December each year. We calculated the annual proportion of patients with at least one outpatient pneumonia (redeemed prescription of relevant antibiotics) or pneumonia hospitalization (hospitalization or ER visit), and stratified by ICS dose (No ICS, low dose, medium dose, or high dose). Results The study population increased from 35,656 patients in 1998 to 99,057 patients in 2018. The annual proportion of patients experiencing a pneumonia decreased from 69.4% to 55.2%. The proportion of patients with at least one outpatient pneumonia, but no hospitalization, decreased (59.2% to 46.2%). The overall proportion of patients with at least one pneumonia hospitalization remained unchanged (10.2% to 9.0%), but this proportion increased in patients in high dose ICS (9.9% to 14.6%). The overall proportion of patients in high dose treatment decreased (12.7% to 5.7%), but not in patients with pneumonia hospitalization (16.5% to 15.1). Conclusions Our study demonstrates a nationwide decrease from 1998 to 2018 in the proportion of patients who redeemed a prescription for antibiotics used mainly for respiratory tract infections, which may reflect a decrease in the number of outpatient pneumonias. This decrease was largely caused by an increase in the number of patients without pneumonia. No differences over time were seen regarding hospitalization-requiring pneumonia. High dose ICS treatment was unchanged in patients with hospitalization-requiring pneumonia.

Urban-rural and socio-economic differences in inhaled corticosteroid treatment for chronic obstructive pulmonary disease: A nationwide register-based cross-sectional study

BackgroundUrban-rural disparities within chronic obstructive pulmonary disease (COPD) have been documented in USA, but not in Europe. Inhaled corticosteroids (ICS) are widely used in COPD despite strict recommendations. We aimed to investigate urban-rural and socioeconomic differences in ICS treatment for COPD. MethodsA Danish nationwide register-based cross-sectional study. All patients alive on the December 31, 2018 with a J44 ICD-10 diagnosis code (COPD) were included (99,057 patients). Daily average ICS dose was calculated from the accumulated ICS use during 2018 based on redeemed prescriptions. Patients were divided into groups: No ICS, low dose ICS, medium dose ICS, high dose ICS. A multinomial logistic regression model including educational level, co-habitation status, age, and sex was performed with “No ICS” as reference group. ResultsCompared to capital municipalities, living in other municipality types was associated with an increased probability of receiving medium and high dose ICS treatment, and increasing odds ratios (ORs) were seen with increasing ICS dose (medium dose ICS: ORs between 1.31 (95 % confidence interval (CI) 1.24–1.38) and 1.35 (95%CI 1.28–1.41), high dose ICS: ORs between 1.73 (95%CI 1.59–1.88) and 1.80 (95%CI 1.68–1.92)). Patients had increased probability of receiving ICS treatment if they were female, were co-habiting, or had completed only primary education. ConclusionPatients with a hospital-registered COPD diagnosis in non-capital municipalities receive more ICS, and in higher doses, compared to patients in capital municipalities. This is the first study to confirm that such urban-rural differences exist in Europe, and further research on this area is warranted.

Response to Biologics and Clinical Remission in the Adult German Asthma Net Severe Asthma Registry Cohort.

Recently, criteria for evaluation of response to biologics have been proposed and the concept of clinical remission has gained attention as a possible goal even in severe asthma. To analyze the response and remission in the German Asthma Net severe asthma registry cohort. We included adults not using a biologic at baseline (V0) and compared patients treated between V0 and 1-year visit (V1) without using a biologic (group A) to patients starting with a biologic after V0 and continuing it up to V1 (group B). We applied the Biologics Asthma Response Score to quantify composite response in good, intermediate, or insufficient. We defined clinical remission (R) as absence of significant symptoms (Asthma Control Test score ≥ 20 at V1) in the absence of exacerbations and oral corticosteroid therapy. Group A included 233 and group B 210 patients, the latter receiving omalizumab (n= 33), mepolizumab (n= 40), benralizumab (n= 81), reslizumab (n= 1), or dupilumab (n= 56). At baseline, group B had less often an allergic phenotype (35.2% vs 41.6%), lower Asthma Control Test score (median, 12 vs 14), more exacerbations in the past year (median, 3 vs 2), and more often high-dose inhaled corticosteroid treatment (71.4% vs 51.5%) than group A. After 1 year of treatment, rates of response (good: 61.4% vs 34.8%; intermediate: 26.7% vs 42.9%; insufficient: 11.9% vs. 22.3%) and/or clinical remission (37.6% vs 17.2%) were higher in group B than in group A. Despite more severe asthma at baseline, patients treated with biologics had a markedly higher probability of achieving good clinical response and/or remission than patients treated without biologics.

Risk factors for nontuberculous mycobacterial pulmonary disease (NTM-PD) in Croatia

The incidence, geographical distribution and clinical relevance of different nontuberculous mycobacteria (NTM) in Croatia are well described. There are few data on the risk factors for developing NTM pulmonary disease (NTM-PD) in this setting. We conducted aretrospective cohort study on all Croatian residents with NTM isolated from respiratory samples in the period from 2006 to 2015 with follow-up to 2018. The American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines were used to establish NTM-PD diagnosis. Clinical, radiological and treatment data were collected from hospital records. Risk analysis calculations were made on the 439 isolation episodes that were classified as definitive NTM-PD (n = 137) or no disease (n = 302). Female gender, presence of bronchiectasis, low BMI and long-term systemic corticosteroid treatment were independent risk factors associated with NTM-PD. Hemoptysis and malaise were presenting symptoms independently associated with NTM-PD. Chronic obstructive pulmonary disease (COPD) and low/moderate dose inhaled corticosteroid (ICS) treatment were not associated with NTM-PD. High dose ICS treatment was asignificant risk factor for developing NTM-PD (aOR = 4.73, CI 1.69-13.23 p = 0.003). The NTM-PD patients in Croatia are similar to those in other published cohorts in terms of their characteristics and risk factors. The significant dose-dependent association between ICS use and NTM-PD adds to the body of evidence suggesting that high dose ICS use is associated with NTM-PD.

Long-term adherence to inhaled corticosteroids in clinical phenotypes of adult-onset asthma

Long-term adherence to inhaled corticosteroids in clinical phenotypes of adult-onset asthma

Characteristics of patients with frequent systemic corticosteroid bursts for asthma in real clinical practice: are there frequent “short bursts?”

Objective The data on intermittent systemic corticosteroid therapy for asthma exacerbation, clinically called a “short burst,” is limited. This study aimed to investigate the characteristics of patients with frequent systemic corticosteroid bursts for asthma in real clinical practice. Methods Consecutive patients who regularly visited our hospital for asthma treatment between January 2019 and December 2020 were reviewed. The number of systemic corticosteroid bursts during the past 1 year was collected, and those with frequent bursts (≥2 times/year) were defined as the Frequent group. Results Data on 236 patients were analyzed. Among them, 5.5% (95% confidence interval 3.2–9.2%) were in the Frequent group. In the Frequent group, 23% of patients had no unplanned visits, and 38% experienced at least one corticosteroid burst without visiting a physician (self-medication). One-third of patients did not undertake high-dose inhaled corticosteroid treatment, and three-fourths of patients did not undertake long-acting muscarinic antagonist treatment. Low pulmonary function and increased blood eosinophils were independently associated with the Frequent group (adjusted odds ratio = 0.73, 95% confidence interval 0.55–0.99, P = 0.039, per 10% predicted increase in a forced expiratory volume in 1 s; adjusted odds ratio = 1.15, 95% confidence interval 1.02–1.29, P = 0.025, per 100/μL increase in blood eosinophils). Conclusions There was a certain rate of frequent corticosteroid bursts in real clinical practice. It is important to determine the actual condition, as some patients experienced “hidden” frequent bursts and have the option to reinforce the treatment.

Short-term responses to high-dose inhaled corticosteroid treatment in patients with chronic obstructive pulmonary disease with a fractional nitric oxide concentration over 35 parts per billion: A single-centre pre–post study

Introduction: There is currently no strategy for identifying chronic obstructive pulmonary disease (COPD) patients whose pulmonary function could benefit from inhaled corticosteroids. We investigated whether a 28-day regime of inhaled corticosteroids improved pulmonary function test results among COPD patients with a fractional exhaled nitric oxide concentration > 35 parts per billion. Methods: This single-centre one-arm pre–post trial included COPD patients with a fractional exhaled nitric oxide concentration > 35 parts per billion treated at our institution from September 2018 to August 2019. Patients were administered budesonide (200 μg, 8 puffs daily) for 28 days. The primary outcome measure was the difference between the forced expiratory volume in 1 s (FEV1) at baseline and after 28 days of inhaled corticosteroid treatment. Secondary outcomes included differences in COPD Assessment Test scores, %FEV1, and that between the percent forced vital capacity (%FVC) at baseline and after 28 days of treatment. Results: Twenty patients completed the 28-day inhaled corticosteroid regime. The mean difference in FEV1 between day 1 and day 28 was 340 mL (95% confidence interval: −100 to 770 mL; p = 0.122). The mean differences in secondary outcomes were: %FVC, −0.16% (95% confidence interval [CI]: −2.84 to 2.53%; p = 0.905); %FEV1, 1.63% (95%CI: −4.56 to 7.81%; p = 0.589); COPD Assessment Test score, −2.50 (95%CI: −5.72 to 0.72; p = 0.121). Conclusion: The 28-day course of inhaled corticosteroids yielded no significant difference in FEV1 for COPD patients with a fractional exhaled nitric oxide concentration > 35 parts per billion. Trial registration: University Hospital Medical Information Network Center, UMIN000034005. Registered 3 September 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000038557

Children with Asthma Have Fixed Airway Obstruction through Childhood Unaffected by Exacerbations

Children with asthma may have a disease course with or without exacerbations, but the relationship between exacerbations and lung function development is poorly understood. To compare lung function trajectories from birth till adolescence in asthmatic children with and without exacerbations. Children with asthma from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) birth cohort had lung function and bronchial reactivity assessed repeatedly from 1 month to 13 years. Exacerbations were diagnosed at the COPSAC clinic defined as symptoms requiring hospitalization, oral or high-dose inhaled corticosteroid treatment. Mixed models were applied to analyze lung function trajectories. Children with asthma with exacerbations (N= 50) had a trajectory of increased, fixed airway obstruction compared with children without exacerbations (N= 47): z-score difference in airway resistance (sRawz) (95% confidence interval [CI]):+0.34 (+0.03;+0.66), P= .03, and maximal mid-expiratory flow (MMEFz):-0.41 (-0.69;-0.13), P= .004, but no differences in forced expiratory volume (FEVz):-0.14 (-0.41;+0.13), P= .29, or bronchial reactivity to methacholine (PDz):+0.08 (-0.26;+0.42), P= .65. This did not change comparing lung function trajectories before and after exacerbations: z-score difference (95% CI) sRawz:-0.04 (-0.35; 0.27), P= .80; MMEFz: 0.01 (-0.02; 0.04), P= .55; FEVz: 0.02 (-0.02; 0.05), P= .42; and PDz:-0.01 (-0.06; 0.05), P= .88. Children with asthma with exacerbations compared with children with asthma without exacerbations are characterized by increased airway obstruction since infancy through childhood. The airway obstruction is a fixed trajectory without progression due to exacerbations, suggesting that exacerbations are a consequence rather than a cause of diminished airway caliber in childhood.

Severe asthma in children-a review of definitions, epidemiology, and treatment options in 2019.

Severe asthma is a relatively uncommon condition in children but one which causes morbidity, occasionally mortality, and is a challenging condition to manage. There are several definitions of severe asthma, which have a common theme of poor control despite high dose inhaled corticosteroid treatment. Depending on the definition chosen, the prevalence of severe childhood asthma may be up to 5% within populations with asthma. Collectively, there is some evidence that the treatments used in severe asthma are beneficial, but a solid evidence-base is lacking for many treatments and some treatments have recognized side effects. Evidence supporting the use of maintenance oral prednisolone and intramuscular triamcinolone is weak. Response to systemic corticosteroids is heterogeneous and recognizing phenotypes or endotypes may identify those most likely to gain maximal benefit from treatment. For children aged 6 to 11 years, the anti-IgE biologic omalizumab is effective and anti-IL-5 agent (mepolizumab) has recently been licenced in Europe (but not the US). Biologics, which are licenced for >11 year olds include omalizumab, mepolizumab, benralizumab, reslizumab, and dupilumab. There is plenty that the clinician can offer to the child and adolescent with severe asthma in 2019, including nontherapeutic and therapeutic interventions. To manage severe asthma, practitioners from broad specialities must establish and maintain a close therapeutic relationship with patients. Looking beyond 2019, more treatment options will emerge for severe childhood asthma, and clinical teams will need to continue weighing up benefits and harms.

EFFICACY OF SUBCUTANEOUS DUPILUMAB A HUMAN ANTI-INTERLEUKIN-4 RECEPTOR ALPHA MONOCLONAL ANTIBODY FOR MODERATE-TO-SEVERE UNCONTROLLED ASTHMATICS.

Introduction For moderate-to-severe persistent asthmatics that remain symptomatic despite their anti-inflammatory high dose inhaled corticosteroid treatment with inhaled long-acting beta2-agonist bronchodilator, the addition of subcutaneous Dupilumab, a fully human anti-interleukin-4 receptor alpha monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling, may provide additional efficacy in sub optimally controlled moderate-to-severe persistent asthmatics. Methods In this open labeled 16-week trial, 60 patients 12 years and older with symptomatic uncontrolled asthma were randomized to receive the addition of subcutaneous Dupilumab at a dose of 300mg every 2 weeks or to continue with their existing therapy. The endpoints of the trial included: FEV1, PEF am, PEF pm, albuterol use, exacerbations rates, and a Quality of life (QOL) questionnaire. Written consent was obtained. Results Mean efficacy measurements at 16 weeks revealed significant improvement in all parameters examined in the treatment group as add-on Dipulimab compared to the group without the add-on therapy. Analysis between both treatment groups revealed significant differences in all parameters monitored (FEV1, PEF am, PEF pm, albuterol use, exacerbations rates, nocturnal awakenings, limited activity, chest tightness, cough, wheezing, shortness of breath) in the group with the add-on Dupilumab. The addition of Dupilumab to the maintenance controller therapy is more effective than the maintenance therapy only. When Dupilumab is added to the maintenance controller therapy, all endpoints significantly improved. Conclusions The addition of subcutaneous Dupilumab has additive beneficial protective effects of bronchodilator, anti-inflammatory and anti-remodeling action, and is safer therapy given the long-term safety issues with high doses of inhaled corticosteroids.

Children with Neutrophil-Predominant Severe Asthma Have Proinflammatory Neutrophils With Enhanced Survival and Impaired Clearance

Airway neutrophils are abundant in some children with severe asthma, but their functions are poorly understood. To characterize that the inflammatory airway environment of children with neutrophil-predominant severe asthma promotes neutrophil survival and disrupts neutrophil-associated innate immune defenses. Sixty-seven children with severe asthma refractory to high-dose inhaled corticosteroid treatment undergoing bronchoscopy with bronchoalveolar lavage (BAL) for clinical indications were stratified into neutrophil "high" versus "low" groups on the basis of BAL differential counts. Neutrophil activation markers, functional assays, and phenotyping studies were performed, as well as airway macrophage functional assays. Results were compared with those from children with moderate asthma treated with inhaled corticosteroids. Children with neutrophil-predominant severe asthma had increased markers of neutrophil activation/degranulation and a greater magnitude of airway proinflammatory cytokine and chemokine release. Primary neutrophils exposed to BAL of these children exhibited greater phagocytic capability and greater neutrophil extracellular trap formation, but a more impaired respiratory burst. Despite greater abundance of airway TGF-β1, the neutrophils were not more apoptotic. Instead, neutrophils had a highly proinflammatory phenotype associated with a number of surface markers that regulate neutrophil activation, recruitment/migration, and granule release. Airway macrophages from children with neutrophil-predominant severe asthma were also more proinflammatory with impaired phagocytosis and increased apoptosis. Children with neutrophil-predominant severe asthma have proinflammatory neutrophils with enhanced survival. Airway macrophages are also proinflammatory and dysfunctional and may contribute to global innate immune impairment. Therapies that target neutrophils and related inflammation may be warranted in this subset of children.

Inhaled corticosteroid normalizes some but not all airway vascular remodeling in COPD.

BackgroundThis study assessed the effects of inhaled corticosteroid (ICS) on airway vascular remodeling in chronic obstructive pulmonary disease (COPD).MethodsThirty-four subjects with mild-to-moderate COPD were randomly allocated 2:1 to ICS or placebo treatment in a double-blinded clinical trial over 6 months. Available tissue was compared before and after treatment for vessel density, and expression of VEGF, TGF-β1, and TGF-β1-related phosphorylated transcription factors p-SMAD 2/3. This clinical trial has been registered and allocated with the Australian New Zealand Clinical Trials Registry (ANZCTR) on 17/10/2012 with reference number ACTRN12612001111864.ResultsThere were no significant baseline differences between treatment groups. With ICS, vessels and angiogenic factors did not change in hypervascular reticular basement membrane, but in the hypovascular lamina propria (LP), vessels increased and this had a proportionate effect on lung air trapping. There was modest evidence for a reduction in LP vessels staining for VEGF with ICS treatment, but a marked and significant reduction in p-SMAD 2/3 expression.ConclusionSix-month high-dose ICS treatment had little effect on hypervascularity or angiogenic growth factors in the reticular basement membrane in COPD, but normalized hypovascularity in the LP, and this was physiologically relevant, though accompanied by a paradoxical reduction in growth factor expression.

Therapeutic implication of genetic variants of IL13 and STAT4 in airway remodelling with bronchial asthma.

Several gene variants identified in bronchial asthmatic patients are associated with a decrease in pulmonary function. The effects of this intervention on pulmonary function have not been fully researched. We determined the effects of high-dose inhaled corticosteroids (ICSs) on decreased pulmonary function in asthmatic Japanese patients with variants of IL13 and STAT4 during long-term treatments with low to mild doses of ICS. In this study, 411 patients with bronchial asthma who were receiving ICSs and living in Japan were recruited, were genotyped, and underwent pulmonary function tests and fibreoptic examinations. The effects of 2 years of high-dose ICSs administered to asthmatic patients who were homozygous for IL13 AA of rs20541 or STAT4 TT of rs925847 and who progressed to airway remodelling were investigated. High-dose ICS treatment increased the pulmonary function of patients homozygous for IL13 AA of rs20541 but not of patients homozygous for STAT4 TT of rs925847. The increased concentrations of the mediators IL23, IL11, GMCSF, hyaluronic acid, IL24, and CCL8 in bronchial lavage fluid (BLF) were diminished after high-dose ICS treatment in patients homozygous for IL13 AA of rs20541. IL13 AA of rs20541 and STAT4 TT of rs925847 are potential genomic biomarkers for predicting lower pulmonary function. The administration of high-dose ICSs to asthmatic patients with genetic variants of IL13 AA may inhibit the advancement of airway remodelling. The genetic variants of STAT4 TT did not respond to high-dose ICSs. Therefore, using medications other than ICSs must be considered even during the initial treatment of bronchial asthma. These genetic variants may aid in the realization of personalized and phenotype-specific therapies for bronchial asthma.

Tiotropium for Adults with Inadequately Controlled Persistent Asthma

To review the literature evaluating the efficacy and steroid-sparing effect of tiotropium for inadequately controlled persistent asthma in adults. Information was obtained through a search of MEDLINE/PubMed (1966-October 2012), using the terms asthma and tiotropium. A further review of reference citations was performed to identify other relevant articles. English-language case reports and clinical trials were reviewed. Publications evaluating the efficacy and steroid-sparing effect of tiotropium in adults with inadequately controlled persistent asthma were included in the review. One case report and 5 clinical trials met our criteria. The ultimate goal for asthma management is to maintain disease control by preventing acute exacerbations while avoiding adverse medication effects. Inhaled corticosteroids (ICS) are part of all preferred maintenance regimens for persistent asthma. Unfortunately, persistent asthma remains inadequately controlled in some patients and concerns about serious adverse effects with long-term high-dose ICS treatment exist. Interest in the use of tiotropium to control asthma symptoms and reduce steroid requirements in inadequately controlled persistent asthma is emerging. Results of several trials indicate that tiotropium improves pulmonary function markers and reduces corticosteroid requirements. Moreover, the largest and longest published trial not only showed improvements in pulmonary function tests but also a reduction in corticosteroid use and an increase in the time to first exacerbation. Although tiotropium use in treatment of persistent asthma appears to be promising, more robust clinical trials are needed to assess whether improved pulmonary function tests as well as a decrease in asthma exacerbations and corticosteroid requirements translate into improvements in quality of life. Additionally, the optimal patient population, long-term efficacy, and safety of tiotropium when delivered by various methods need to be determined before it can be recommended over current alternative asthma therapies.

Identifying problematic severe asthma in the individual child – does lung function matter?*

Measures of lung function (usually FEV(1) <80% predicted) are used to classify asthma severity in both adults and children, despite evidence that lung function impairment is less pronounced in the paediatric asthma population. The present study assesses the relevance of lung function measurements as discriminators of severe childhood asthma. Fifty-one school-aged children with problematic severe asthma, 37 mild-to-moderate asthmatics and 29 healthy controls underwent a comprehensive clinical work-up. Problematic severe asthma was defined in patients exhibiting poor asthma control despite high-dose inhaled corticosteroid treatment and at least one other asthma controller drug. Mild-to-moderate asthmatic children used low-dose inhaled steroids and reported minimal asthma symptoms. Baseline FEV(1) values were significantly reduced in children with problematic severe asthma, yet FEV(1) <80% predicted showed a low sensitivity (41%) for discriminating severe vs. mild-to-moderate asthma. Receiver-operated characteristic analysis estimated the optimal cut-off of FEV(1) to be 90% predicted in this population (sensitivity 61%, specificity 83%). Baseline FEV(1)/FVC and FEF(25-75) values were not superior to FEV(1) in discriminating problematic severe asthma, and neither exhaled nitric oxide levels nor bronchial hyperresponsiveness differentiated between the two asthmatic study populations. Spirometric measurements are insensitive discriminators of problematic severe asthma in childhood.

Effect of therapeutic doses of mometasone furoate on cortisol levels in children with mild asthma

Corticosteroids are the foundation of pharmacologic treatment for children with asthma. However, high-dose inhaled corticosteroid treatment can cause hypothalamic-pituitary-adrenal (HPA) axis suppression. We investigated the effect of three doses of mometasone furoate administered via dry-powder inhaler (MF-DPI) on the HPA axis in children. Fifty children (6-11 years) with mild asthma of > or =6 months' duration were randomized to MF-DPI, 100 (n = 13), 200 (n = 13), or 400 micrograms b.i.d. (n = 12), or placebo (n = 12) for 29 days. The primary end point was change from baseline in the 12-hour area under the plasma-cortisol-concentration-time curve (AUC). Secondary parameters included plasma cortisol response to cosyntropin stimulation and 24-hour urinary free cortisol concentrations. Compared with placebo, AUC changes associated with treatments of MF-DPI, 100 or 200 micrograms b.i.d., were not significant, whereas a significant change was observed with MF-DPI, 400 micrograms b.i.d. (27%; p = 0.05). Responses to cosyntropin stimulation and urinary cortisol measurements were similar to placebo with all MF-DPI doses. All regimens were well tolerated. MF-DPI did not have a significant effect on plasma or urinary cortisol levels at doses up to 200 micrograms b.i.d. in children with mild asthma. Higher MF-DPI doses may potentially suppress the HPA axis.

Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment

Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment

Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment

Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment

Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide

Children with severe asthma have persistent symptoms despite treatment with inhaled corticosteroids (ICSs). The differentiating features of severe asthma in children are poorly defined. To identify features of severe versus mild-to-moderate asthma in school-age children using noninvasive assessments of lung function, atopy, and airway inflammation. A total of 75 children (median age, 10 years) with asthma underwent baseline characterization including spirometry and lung volume testing, methacholine bronchoprovocation, allergy evaluation, and offline measurement of exhaled nitric oxide (F(ENO)). Twenty-eight were followed longitudinally over 6 months. Participants were assigned to the severe asthma subgroup if they required high-dose ICS plus 2 or more minor criteria. Children with severe versus mild-to-moderate asthma had more symptoms, greater airway obstruction, more gas trapping, and increased bronchial responsiveness to methacholine. Subjects with severe asthma also had higher concentrations of F(ENO) and significantly greater sensitization to aeroallergens. With long-term study, both the reduction in FEV(1) and increase in F(ENO) persisted in the severe versus mild-to-moderate group. Furthermore, despite adjustments in ICS doses, the frequency of exacerbations was significantly higher in subjects with severe (83%) versus mild-to-moderate asthma (43%). Severe asthma in childhood is characterized by poor symptom control despite high-dose ICS treatment and can be differentiated from mild-to-moderate asthma by measurement of lung function and F(ENO). Clinicians should suspect severe asthma in children with poor response to ICS, airway obstruction, and high F(ENO).

Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment

The role of inhaled corticosteroids in the management of chronic obstructive pulmonary disease (COPD) remains controversial. The purpose of this study was to evaluate whether sputum eosinophilia (defined as eosinophils > or = 3%) predicts clinical benefit from inhaled corticosteroid treatment in patients with smoking-related clinically stable moderate-to-severe COPD. Forty consecutive patients with effort dyspnoea (mean age 67 yrs; 52 pack-yr smoking history; post-bronchodilator forced expiratory volume in one second (FEV1) <60% predicted, consistent with moderate-to-severe smoking-related chronic airflow limitation) were enrolled. Subjects were treated with inhaled placebo followed by inhaled budesonide (Pulmicort Turbuhaler 1,600 microg.day(-1)), each given for 4 weeks. While the treatment was single-blind (subject level), sputum cell counts before and after treatment interventions were double-blind, thus removing bias. Outcome variables included spirometry, quality-of-life assessment and 6-min walk test. Sputum eosinophilia was present in 38% of subjects. In these, budesonide treatment normalised the eosinophil counts and, in comparison to placebo treatment, resulted in clinically significant improvement in the dyspnoea domain of the disease-specific chronic respiratory questionnaire (0.8 versus 0.3) and a small but statistically significant improvement in post-bronchodilator spirometry (FEV1 100 mL versus 0 mL; p<0.05). In conclusion, sputum eosinophilia predicts short-term clinical benefit from high-dose inhaled corticosteroid treatment in patients with stable moderate-to-severe chronic obstructive pulmonary disease.