Mild-moderate Persistent Asthma Research Articles

A Single Inhaler Combining a Corticosteroid and Long-Acting Beta-2 Agonist for Maintenance with Additional Doses for Reliever Therapy (SMART): Obstacles for Asthma Patients in the USA.

A Single Inhaler Combining a Corticosteroid and Long-Acting Beta-2 Agonist for Maintenance with Additional Doses for Reliever Therapy (SMART): Obstacles for Asthma Patients in the USA.

Ultraviolet Irradiation Units Installed In the Homes of Children With Asthma Reduces Asthma Severity

Multifaceted environmental control interventions recommended as part of asthma management can be costly and difficult to maintain. The objective of this study was to determine if the novel CREON2000A ultraviolet (UV) air irradiation system technology (General Innovation & Goods. Inc.) used as a single environmental intervention would reduce asthma severity in children with mild-moderate persistent asthma.

Neighborhood Social Conditions, Family Relationships, and Childhood Asthma

E Chen, R Hayen, V Le. Pediatrics . 2019;144(2):e20183300 To determine if positive family relationships mitigate the negative impact that residing in a dangerous neighborhood can have on asthma. In total, 308 children (age 9–17 years) with physician-diagnosed asthma living in the Chicago area were studied. The majority (70%) had mild-moderate persistent asthma, and 14% had severe asthma. Exclusion criteria included other chronic diseases and acute respiratory illness. This was a cross-sectional, observational study. Neighborhood danger was assessed by two raters who observed subjects’ neighborhoods on Google Earth Pro and Google Street View Imagery. Signs of physical disorder (litter, graffiti, …

Value of bronchial reversibility to salbutamol, exhaled nitric oxide and responsiveness to methacholine to corroborate the diagnosis of asthma in children

Introduction and ObjectivesFunctional and inflammatory measures have been recommended to corroborate asthma diagnosis in schoolchildren, but the evidence in this regard is conflicting. We aimed to determine, in real-life clinical situation, the value of spirometry, spirometric bronchial reversibility to salbutamol (BDR), bronchial responsiveness to methacholine (MCT) and fractional exhaled nitric oxide (FENO), to corroborate the diagnosis of asthma in children on regular inhaled corticosteroids (ICS) referred from primary care. MethodsOne hundred and seventy-seven schoolchildren with mild-moderate persistent asthma, on treatment with regular ICS, participated in the study. Abnormal tests were defined as FENO ≥ 27 ppb, BDR (FEV1 ≥ 12%) and methacholine PC20 ≤ 4 mg/mL. ResultsThe proportions of positive BDR, FENO and MCT, were 16.4%, 33.3%, and 87.0%, respectively. MCT was associated with FENO (p < 0.03) and BDR (p = 0.001); FENO was associated with BDR (p = 0.045), family history of asthma (p = 0.003) and use of asthma medication in the first two years of life (p = 0.004). BDR was significantly related with passive tobacco exposure (p = 0.003). ConclusionsSpirometry, BDR and BDR had a poor performance for corroborating diagnosis in our asthmatic children on ICS treatment; on the contrary, MCT was positive in most of them, which agrees with previous reports. Although asthma tests are useful to corroborate asthma when positive, clinical diagnosis remains the best current approach for asthma diagnosis, at least while better objective and feasible measurements at the daily practice are available. At present, these tests may have a better role for assessing the management and progression of the condition.

Caregiver and pediatric provider perspectives on symptom-based inhaled corticosteroid therapy in asthma

Guidelines recommend that healthcare providers adjust the dose of inhaled corticosteroids (ICS) in asthma patients based on the degree of symptom severity and control. Symptom-based, intermittent ICS therapy (use of ICS together with short acting bronchodilators- symptom-based adjustment: SBA) has been demonstrated to be comparable to guideline-based management by providers in controlled clinical trials. We sought input from African American caregivers and pediatricians on the acceptability and barriers for this alternative management strategy. Focus group interviews of caregivers and individual interviews with community providers of African-American children ages 6-17 years with mild-moderate persistent asthma were conducted by trained facilitators to assess perceptions of how asthma affects children and their caregivers, and of SBA as a management strategy. Interview data were transcribed and analyzed using inductive thematic based coding. Twenty-six parents participated in six focus groups. Fourteen pediatricians were interviewed. Caregivers reported facing financial burden and difficulty with tracking medications. Caregivers and pediatricians were favorable about SBA, citing its potential for decreased use of medications and cost and similarity to actual care provided. Some caregivers voiced concern that SBA would not be as effective as daily ICS. Caregivers suggested that education on symptom recognition and close communication between physician and patient would facilitate the implementation of SBA. SBA was generally viewed favorably by caregivers and providers of African American children. However, concerns regarding effectiveness of SBA were voiced by both caregivers and providers. Patient education and provider-patient communication is important in implementing this alternative asthma management strategy.

Effects of Mometasone, Fluticasone, and Montelukast on Bone Mineral Density in Adults with Asthma

Associations of inhaled corticosteroids (ICS) with bone mineral density (BMD) loss have not been characterized consistently. This randomized, double-blind study assessed effects of mometasone furoate (MF) administered via dry powder inhaler on BMD of patients with persistent asthma. Adults with mild-moderate persistent asthma who did not receive ICS for ≥3 months were randomized to MF 400 μg once daily (QD) in the evening (pm), MF 200 μg QD pm, montelukast sodium (ML) 10 mg QD pm, or fluticasone propionate (FP) 250 μg twice daily. Included patients had 25-hydroxy vitamin D levels ≥15 ng/mL at baseline. All the patients received calcium and vitamin D supplements for daily use during the trial. Duplicate BMD scans were done at baseline, 6 months, and 1 year. The mean percentage change in lumbar spine (LS) BMD from baseline to end point for MF 400 μg versus ML 10 mg was the primary analysis. Changes from baseline in left total femur BMD and femoral neck BMD were secondary assessments. At the end point, mean LS BMD increased 0.9% (MF 400 μg), 1.2% (ML), 0.7% (MF 200 μg), and 1.1% (FP), with no significant differences for MF 400 μg versus ML (-0.3% [95% CI, -1.01 to 0.27]) for LS BMD. No significant differences among treatments occurred for changes in left total femur BMD; all were slight increases. Changes in femoral neck BMD were 0.4% (MF 400 μg), -0.2% (ML), -0.2% (MF 200 μg), and -0.4% (FP); only the difference between MF 400 μg and FP was statistically significant (P = .044). No detrimental effects on lumbar BMD were observed after up to 1 year of treatment with MF in comparison with ML for patients who received calcium and vitamin D supplements.

Serum immunoglobulin levels as a predictive factor for a better outcome of non-atopic childhood asthma

Childhood asthma is a heterogeneous condition with different phenotypes. Hereby, we aimed to study impact of serum immunoglobulin levels on clinical phenotypes and outcome of asthma. Seventy-eight children (M: 26, F: 52) aged less than 10 yrs (mean = 8.56 ± 3.23 yrs) and diagnosed as mild-moderate persistent asthma, followed up for at least 1 yr were included into the study. Asthmatic children were divided into two groups based on serum immunoglobulin levels at admission and were evaluated with respect to demographic data, allergic sensitization, symptom scores, medication usage, pulmonary functions, and non-specific bronchial hyper-reactivity. The age at onset of symptoms (40.88 ± 32.02 vs. 23.04 ± 26.97 months) was significantly younger in children with hypogammaglobulinemia (n = 28) compared to normogammaglobulinemia group (n = 50) (p = 0.016). Mean follow-up duration was 3.8 ± 2.1 yrs. Atopic sensitization rate was higher in those with normal immunoglobulin levels (81.2% vs. 17.9%), (p < 0.0001). Normal serum immunoglobulin levels were associated with atopic asthma (OR, 4.5; 95% confidence interval (CI): 2.0-10.1). For the prediction of atopic asthma, having normal immunoglobulin levels yielded predictive values of: sensitivity = 88.6%, specificity = 71.8%, positive predictive value = 81.1%, negative predictive value = 82.1%. Furthermore, percentages of atopic dermatitis and allergic conjunctivitis, elevated serum total IgE levels, eosinophilia, and bronchial hyper-reactivity were more common in normogammaglobulinemia with asthma group (p = 0.040, p = 0.003, p = 0.024, p = 0.030, p = 0.040, respectively). Although marked reductions in asthma scores and inhaled corticosteroid usage were observed in both groups over time, the rate of decline was significantly higher and earlier in hypogammaglobulinemia group (p = 0.0001, p = 0.004, respectively). In conclusion, asthmatic children with hypogammaglobulinemia presented at an earlier age, with lower rates of atopy, and earlier clinical improvement accompanied with earlier discontinuation of inhaled corticosteroids than children with normal immunoglobulin levels. Our data demonstrated that in children currently named as early-onset non-atopic asthma, hypogammaglobulinemia might be accompanying, providing evidence for a different phenotype of childhood asthma.

Neutrophilic Cells in Sputum of Allergic Asthmatic Children

Airway inflammation is regarded as a central feature of asthma and is mostly sustained by eosinophilic infiltrate. Recent studies have shown that a co-activation of eosinophil- and neutrophil-dependent inflammatory mechanisms might explain why some asthmatics do not respond to conventional asthma therapy. The aim of our study is to determine whether neutrophilic inflammation was involved in 55 allergic children with mild-moderate persistent asthma and the relationship with the response to steroid treatment. Before the sputum analysis, all children underwent spirometry with the reversibility test, and were divided into two groups on the basis of the response (such as &gt;12% of baseline FEV1): group 1 positive and group 2 negative. Eosinophil cationic protein concentrations were measured by radioimmunoassay and neutrophyl myeloperoxidase (MPO) concentrations were measured by an MPO-EIA. Ten healthy children of comparable ages served as control group. Total IgE, FEV1 and FEV/FVC values were similar in both groups. The sputum macrophage count was higher in controls than in allergic asthmatics, but there was no difference between groups 1 and 2 (59.6% vs 18.3% and 17%; p≤ 0.005). Sputum neutrophils were significantly higher in group 2 both vs controls (62% vs 34%; p≤ 0.005) and vs group 1 (62% vs 37%; p≤ 0.005). Our data suggest that neutrophils are involved in airway allergic inflammation in mild-moderate persistent childhood asthma and a high neutrophil count in sputum may be related to a lower responsiveness to inhaled corticosteroids.

Comparative effect of body mass index on response to asthma controller therapy

Increases in body mass index (BMI) are reported to influence asthma severity and response to treatment. This analysis was designed to explore whether increasing BMI altered the comparative response to treatment with either fluticasone propionate (FP) or montelukast. Two double-blind, randomized, parallel-group trials of 12-weeks duration comparing FP, 88 micrograms, twice daily or montelukast, 10 mg, daily were evaluated. Subjects with mild-moderate persistent asthma were retrospectively stratified by BMI of <20 kg/m(2) (underweight), 20-24.9 kg/m(2) (normal weight), 25-29.9 kg/m(2) (overweight), and > or =30 kg/m(2) (obese). Outcomes included mean changes in forced expiratory volume in 1 second (FEV(1)) and morning peak flow, daily albuterol use, and daily symptom scores. There were 1052 subjects evenly distributed between FP and montelukast by baseline parameters, including BMI. FP was statistically superior to montelukast for all BMI categories of normal, overweight, and obese subjects for FEV(1) (p < 0.008), morning peak flow (p < 0.002), albuterol use (p < 0.02), and symptom scores (p < 0.05). FP produced a significantly greater clinical response for normal, overweight, and obese subjects compared with montelukast. Irrespective of BMI, FP appears to be the more effective asthma controller therapy.

The role of inhaled corticosteroids and montelukast in children with mild–moderate asthma: results of a systematic review with meta-analysis

ObjectiveTo compare the efficacy of inhaled corticosteroids (ICS) versus montelukast (MONT) in schoolchildren and adolescents with mild–moderate persistent asthma.MethodsRandomised, prospective, controlled trials published January 1996 to November 2009 with a...

Non-corticosteroid therapy for the long-term control of asthma

The non-corticosteroids approved for the maintenance therapy of persistent asthma include the long-acting inhaled β2 agonists (LABAs), leukotriene modifiers, chromones, theophylline and omalizumab. This review assesses the benefits and risks of each in relation to the inhaled corticosteroids and each other. Neither the LABAs nor omalizumab should be used as monotherapy for persistent asthma. There is no evidence of clinically significant differences in efficacy between the chromones, theophylline and leukotriene modifiers as monotherapy in mild-moderate persistent asthma; thus the choice of one therapy over the other is a clinical decision based upon differences in safety, acceptability to the patient and ease of use. Although there is significant variability in response to various therapies, non response to one therapy is not predictive of response to another. Neither studies of phenotypes nor genotypes have provided acceptable determinants of response as yet. As adjunctive therapy to the inhaled corticosteroids for moderate-severe persistent asthma, the LABAs provide superior improvement in lung function and reduction in exacerbations relative to higher doses of inhaled corticosteroids and the other noncorticosteroids used as adjunctive therapy. Thus, LABAs remain the adjunctive therapy of choice in patients not adequately controlled on low-medium dose inhaled corticosteroids. Omalizumab has not been compared with the other adjunctive therapies, so its relative efficacy is unknown. However, it is the only adjunctive therapy added to the combination of an inhaled corticosteroid plus LABA to demonstrate further improvement in a controlled clinical trial.

Patient preferences for managing asthma: results from a discrete choice experiment

Effective control of asthma requires regular preventive medication. Poor medication adherence suggests that patient preferences for medications may differ from the concerns of the prescribing clinicians. This study investigated patient preferences for preventive medications across symptom control, daily activities, medication side-effects, convenience and costs, using a discrete choice experiment embedded in a randomized clinical trial involving patients with mild-moderate persistent asthma. The present data were collected after patients had received 6 weeks' treatment with one of two drugs. Three choice options were presented, to continue with the current drug, to change to an alternative, hypothetical drug, or to take no preventive medication. Analysis used random parameter multinomial logit. Most respondents chose to continue with their current drug in most choice situations but this tendency differed depending on which medication they had been allocated. Respondents valued their ability to participate in usual daily activities and sport, preferred minimal symptoms, and were less likely to choose drugs with side-effects. Cost was also significant, but other convenience attributes were not. Demographic characteristics did not improve the model fit. This study illustrates how discrete choice experiments may be embedded in a clinical trial to provide insights into patient preferences.

Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: The Pediatric Asthma Controller Trial

More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children. The Pediatric Asthma Controller Trial (PACT) compared the effectiveness of 3 regimens in achieving asthma control. A total of 285 children (ages 6-14 years) with mild-moderate persistent asthma on the basis of symptoms, and with FEV(1) >or= 80% predicted and methacholine FEV(1) PC(20) <or= 12.5 mg/mL, were randomized to 1 of 3 double-blind 48-week treatments: fluticasone 100 microg twice daily (fluticasone monotherapy), fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening (PACT combination), and montelukast 5 mg in the evening. Outcomes included asthma control days (primary outcome), exacerbations, humanistic measurements, and pulmonary function measurements. Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes, including percent of asthma control days, but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity (P = .015), maximum bronchodilator response (P = .009), exhaled nitric oxide (P < .001), and PC(20) (P < .001). Fluticasone monotherapy was superior to montelukast for asthma control days (64.2% vs 52.5%; P = .004) and for all other control outcomes. Growth over 48 weeks was not statistically different (fluticasone, 5.3 cm; PACT combination, 5.3 cm; montelukast, 5.7 cm). Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast. However, fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control. Growth was similar in all groups. Therefore, of the regimens tested, the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1) >or= 80% predicted, confirming current guideline recommendations.

Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma?

Background: Exercise can alter health in children in both beneficial (eg reduced long-term risk of atherosclerosis) and adverse (eg exercise-induced asthma) ways. The mechanisms linking exercise and health are not...

Is there a difference between chronic airway inflammation in chronic severe asthma and chronic obstructive pulmonary disease?

The lack of a universally accepted definition of chronic severe asthma and the continuous changes in the classification of the severity of stable chronic obstructive pulmonary disease in the last 10 years make it difficult to compare the many studies available. The aim of the review is to compare studies on chronic severe asthma that have a control group of patients with mild to moderate persistent asthma and studies on stable chronic obstructive pulmonary disease that have an age-matched control group of smokers with normal lung function (with or without chronic bronchitis). Our review of the recent literature in this field seems to indicate that chronic airway inflammation in chronic severe asthma is characterized in most cases, both in central and peripheral airways, by the same pathological features of mild-moderate persistent asthma with an increased number of activated T lymphocytes, particularly CD4 Th2 cells, and sometimes eosinophils and mast cells. The most notable difference of chronic severe asthma compared with mild to moderate disease is the increased number of neutrophils. Chronic airway inflammation in stable chronic obstructive pulmonary disease is characterized, both in central and peripheral airways, by an increased number of T lymphocytes, particularly CD8+, macrophages and neutrophils. Macrophage and neutrophil counts increase with the progression of the severity of the disease. These differences in chronic airway inflammation support the consensus that asthma and chronic obstructive pulmonary disease are different diseases along all their stages of severity.

Serum interleukin-5 levels are elevated in mild and moderate persistent asthma irrespective of regular inhaled glucocorticoid therapy.

BackgroundInterleukin-5 (IL-5) is thought to play a pivotal role in the pathogenesis of asthma. High levels of circulating IL-5 have been documented in acute asthma. However, serum IL-5 levels in mild to moderate asthmatics and the influence of regular use of inhaled glucocorticoids, is not known.MethodsFifty-six asthmatics and 56 age and sex matched controls were recruited prospectively from an outpatient department. Information on asthma severity and treatment was gathered by a questionnaire. Serum IL-5, total IgE and specific IgE levels were measured in a blinded fashion.ResultsThere were 32 atopic and 24 non-atopic mild-to-moderate asthmatics. The median serum IL-5 levels in atopic asthmatics (9.5 pg/ml) and in non-atopic asthmatics (8.1 pg/ml) were significantly higher than in normal controls (4.4 pg/ml, both p < 0.003). However, median serum IL-5 levels in atopic and non-atopic asthmatics were not significantly different. The median serum IL-5 level was insignificantly higher in fourteen moderate persistent asthmatics (10.6 pg/ml) compared to forty-two mild persistent asthmatics (7.3 pg/ml) (p = 0.13). The median serum IL-5 levels in asthmatics using regular inhaled steroids (7.8 pg/ml) was not significantly different from those not using inhaled steroids (10.2 pg/ml). Furthermore, serum total IgE levels and eosinophil counts were not significantly different in those using versus those not using inhaled glucocorticoids.ConclusionSerum IL-5 levels are elevated in mild and moderate persistent atopic and non-atopic asthmatics. Regular use of inhaled glucocorticoids may not abrogate the systemic Th2 type of inflammatory response in mild-moderate persistent asthma.

Growth and bone density in children with mild-moderate asthma: A cross-sectional study in children entering the Childhood Asthma Management Program (CAMP)

Objectives We sought to determine whether mild-moderate persistent asthma sufficient to produce a decrease in baseline lung function is associated with an adverse effect on growth and bone mineral density (BMD) in children. Methods This was a cross-sectional study of 1041 children, 5 to 12 years old (32% ethnic/racial minorities and 40% female), enrolled into the Childhood Asthma Management Program (CAMP). Measures of asthma severity included: Spirometry; bronchial hyperresponsiveness; duration of asthma symptoms; and symptom-based assessment of severity. Multiple regression analyses were used to relate the asthma severity on the primary outcome variables: Height by stadiometry and BMD by dual energy radiographic absorptiometry. Results The mean ± SD height percentile was 56.0 ± 28.5 percentile for the population. The only significant relationship between asthma severity and height percentile was with methacholine bronchoprovocation in girls (β 2.98, P = .019, covariate multiple regression). The mean ± SD BMD was 0.65 ± 0.10 g/cm2 for the population. The past use of corticosteroids did not adversely affect either growth or BMD. Conclusions We found that mild-moderate asthma of as long as 4 to 7 years duration in children does not produce an adverse effect on linear growth or BMD. (J Pediatr 2003;142:286-91)

Comparison of montelukast and budesonide on bronchial reactivity in subjects with mild-moderate persistent asthma

We studied 51 atopic non-smoking subjects who were divided to four treatments groups: (A) montelukast 10 mg daily, (B) budesonide 400 μg twice a day (bid), (C) montelukast 10 mg daily plus budesonide 400 μg bid and (D) budesonide 800 μg bid. Bronchial responsiveness was assessed before and after 12 weeks of treatment. The bronchial responsiveness, evaluated by means of PC 20 values, showed a strong significant increase in groups B, C and D, and a weak but significant rise in group A, when compared to basal data. Regarding other pulmonary parameters (FEV 1, PEF) there were no significant differences among the groups after 12 weeks of therapy. A statistical significance was founded after therapy between group A and C ( p<0.05), but not between the group B and D treated with only budesonide at different doses. No significant differences was observed in the side effect pattern among the various treatments. The study data demonstrated that administration of montelukast provided an important and additional effect on bronchial hyperresponsiveness. Oral administration represents a significant advantage over the majority of other anti-asthmatic drugs. Our results confirm the anti-inflammatory properties of both the inhaled corticosteroid (ICS) and montelukast and the possible role of these drugs can have on airway remodelling. While currently low dose ICS remains the reference drug as a controller in mild-moderate persistent asthma, montelukast may be viewed as a possible option, either in monotherapy or in association.