Corticosteroids For Treatment Of Asthma Research Articles

The Role of Upper Airway Microbiome in the Development of Adult Asthma.

Clinical and molecular phenotypes of asthma are complex. The main phenotypes of adult asthma are characterized by eosinophil and/or neutrophil cell dominant airway inflammation that represent distinct clinical features. Upper and lower airways constitute a unique system and their interaction shows functional complementarity. Although human upper airway contains various indigenous commensals and opportunistic pathogenic microbiome, imbalance of this interactions lead to pathogen overgrowth and increased inflammation and airway remodeling. Competition for epithelial cell attachment, different susceptibilities to host defense molecules and antimicrobial peptides, and the production of proinflammatory cytokine and pattern recognition receptors possibly determine the pattern of this inflammation. Exposure to environmental factors, including infection, air pollution, smoking is commonly associated with asthma comorbidity, severity, exacerbation and resistance to anti-microbial and steroid treatment, and these effects may also be modulated by host and microbial genetics. Administration of probiotic, antibiotic and corticosteroid treatment for asthma may modify the composition of resident microbiota and clinical features. This review summarizes the effect of some environmental factors on the upper respiratory microbiome, the interaction between host-microbiome, and potential impact of asthma treatment on the composition of the upper airway microbiome.

Nasal gene expression changes with inhaled corticosteroid treatment in asthma

Nasal gene expression changes with inhaled corticosteroid treatment in asthma

The role of fractional exhaled nitric oxide in the diagnosis and monitoring of respiratory disease

Recent guidelines have suggested the use of fractional exhaled nitric oxide in the diagnosis and monitoring of respiratory disease. Aleksandra Gawlik-Lipinski explains the evidence behind this testing Fractional exhaled nitric oxide (FeNO) is linked to the inflammatory process in the lungs and levels are typically elevated in the eosinophilic asthma phenotype. Therefore, FeNO is useful in the diagnosis of asthma and there is an indication that it could guide corticosteroid treatment in asthma and chronic obstructive pulmonary disease (COPD) patients with eosinophilic inflammation patterns of disease. There is also limited evidence suggesting that FeNO could aid differentiating between asthma, COPD and asthma–COPD overlap. More research is required to establish the role of FeNO measurement in other respiratory diseases.

O-41 Pharmacogenomic studies of corticosteroid effectiveness in paediatric asthma: a systematic review

Background Genetic variations has the potential to al-ter therapeutic efficacy. The aim of the study is to analyse polymorphisms associated with variation in response to corticosteroid treatment in paediatric asthma patients. Asthma is one of the most common chronic respiratory diseases in childhood, with about 300 million asthmatic patients worldwide and a sharp increase in their preva-lence. Despite corticosteroids being highly effective for the chronic treatment of asthma, there are variations in therapeutic responsiveness. These variations can be at-tributed to a degree of heterogeneity, which is associated in part to genetic variation. This provide the rationale for pharmacogenetic studies of corticosteroids. Methods Relevant literature was identified through CENTRAL, CINAHL, MEDLINE and Scopus. Studies in which pharmacogenetic methods, such as genome-wide association studies, candidate gene studies and genome sequencing, were used to identify and repeatedly vali-date the effect of one or more single nucleotide polymor-phisms on the efficacy of inhaled corticosteroids. Results The search returned 341 studies, with 23 full text articles assessed for eligibility. We excluded 14 full text articles with the remaining 9 studies included (incorpo-rating analysis of 210 SNPs and including in over 7000 children). Variants that enhanced response to cortico-steroids include CRHR1 (rs1876828), T gene (rs3127412 and rs6456042), TBX21 gene (rs2240017) in TXB21 gene, ORMDL3 (rs2872507). Genes containing polymorphisms predictive of reduced response to corticosteroids were FCER2 (rs28364072) and ST13 (rs138335 and sr138337), and GLCCI1 (rs37972). Successful replication of CRHR1 and FCER2 in additional publications has been achieved, but GLCCI1 was not successfully replicated. Various out-come measures were used across the studies. Conclusion Numerous SNPs that alter the effectiveness of corticosteroid treatment in asthma have been identi-fied, but external replication has been limited to date, and application into clinical practice is not routine.

Effect of obesity on sinonasal disease in asthma

ABSTRACTObjective: Sinonasal disease can contribute to poor asthma control. There are reports that link obesity with an increased prevalence of sinonasal disease, but no studies evaluating the severity of sinonasal disease in obese asthmatics, and how this impacts asthma control. The purpose of the current study was to determine if obesity is associated with increased severity of sinonasal disease, and/or affects response to nasal corticosteroid treatment in asthma. Methods: This study included 236 adults participating in a 24-week randomized, double-masked, placebo-controlled study of nasal mometasone for the treatment of poorly controlled asthma. Sinonasal disease severity was assessed using validated questionnaires, and compared in participants of differing BMIs. Eosinophilic inflammation was assessed using markers in nasal lavage, serum and exhaled nitric oxide. Response to treatment was compared in different BMI groups. Results: Obesity had no effect on the severity of sinonasal disease symptoms in asthmatics (Sino-Nasal Outcome Test 22 (SNOT 22) score [mean ± SD] 35.4 ± 18.5, 40.2 ± 22.8, and 39.1 ± 21.7, p = 0.43, in lean, overweight and obese participants), nor on nasal, bronchial or systemic markers of allergic inflammation. Nasal steroids had some limited effects on symptoms, lung function and inflammatory markers in lean participants, but no detectable effect was found in obese patients. Conclusions: Obesity does not affect severity of sinonasal disease in patients with asthma; the association of sinonasal disease symptoms with increased asthma severity and markers of Type 2 inflammation are consistent across all BMI groups. The response of obese patients to nasal corticosteroids requires further study.

Periostin levels and eosinophilic inflammation in poorly-controlled asthma.

BackgroundPeriostin levels are associated with airway eosinophilia and are suppressed by corticosteroid treatment in asthma. This study sought to determine the relationship between serum and sputum periostin, airway inflammatory phenotype and asthma control.MethodsAdults with poorly-controlled asthma (n = 83) underwent a clinical assessment, sputum induction and blood sampling. Dispersed sputum was used for a differential cell count and periostin assessment (ELISA). Serum periostin was determined by the Elecsys® immunoassay.ResultsPeriostin levels were significantly higher in serum (median (IQR) of 51.6 (41.8, 62.6) ng/mL) than in sputum (1.1 (0.5, 2.0) ng/mL) (p < 0.001). Serum and sputum periostin were significantly higher in patients with eosinophilic asthma (n = 37) compared with non-eosinophilic asthma. Both serum and sputum periostin levels were significantly associated with proportion of sputum eosinophils (r = 0.422, p < 0.001 and r = 0.364, p = 0.005 respectively) but were not associated with asthma control. In receiver operator characteristic curve analysis, the area under the curve (AUC) for serum periostin (n = 83) was 0.679, p = 0.007. Peripheral blood eosinophils assessed in 67 matched samples, had a numerically greater AUC of 0.820 compared with serum periostin, p = 0.086 for the detection of eosinophilic asthma.ConclusionIn poorly-controlled asthma, sputum and serum periostin levels are significantly related to sputum eosinophil proportions while their ability to predict the presence of eosinophilic asthma is modest.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0230-4) contains supplementary material, which is available to authorized users.

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.

Evolution of Human Herpesvirus Type 8-associated Gastric Kaposi's Sarcoma Following Corticosteroid Treatment for Asthma

The association of gastric Kaposi's sarcoma (KS) with human herpesvirus type 8 (HHV-8) may be found in immunosuppressed patients such as those with AIDS or transplant recipients. A 64-year-old man with a 2-year history of corticosteroid treatment was admitted due to the impression of chronic obstructive pulmonary disease with secondary infection. Abdominal fullness and tarry stool led to the performance of panendoscopy, which revealed two hypertrophic gastric mucosal lesions. These lesions had transformed into a large polyp 2 months later. KS was not diagnosed until a third endoscopic biopsy was performed. The polyp further transformed into a flattened, elongated tumor within a month. The patient died from acute cardiopulmonary insufficiency 4 days after radical gastrectomy. Polymerase chain reaction study identified HHV-8 in all biopsied specimens and resected tumor lesions. Immunostaining further demonstrated the virus in the tumor cells. Both of these methods seemed more sensitive in diagnosing KS than histologic examination of small biopsied specimens. This case suggests the existence of a relationship between gastric KS and HHV-8 infection.

Asthma and Therapeutics: Inhaled Corticosteroids, Corticosteroid Osteoporosis, and the Risk of Fracture in Chronic Asthma

Current guidelines for the diagnosis and treatment of osteoporosis do not address the risks to bone density and the likelihood of fracture that may be associated with inhaled corticosteroid treatment for asthma. This review outlines an approach to the use of bone densitometry in clinical practice for the diagnosis, prevention, and treatment of osteoporosis in asthmatic patients receiving inhaled corticosteroid therapy.

Hypertonicity of the challenge solution may increase the diagnostic accuracy of histamine challenge

There is significant overlap in the responsiveness to direct airway challenges, such as the histamine challenge, between asthmatic and non-asthmatic subjects, which decreases their accuracy in the diagnosis of asthma. To minimise this overlap, a new test, hypertonic histamine challenge, was developed. Fifteen healthy subjects, 16 subjects with steroid-naive asthma, and 16 asthmatic subjects undergoing inhaled corticosteroid treatment underwent inhalation challenges with hypertonic saline, isotonic histamine, and hypertonic histamine, using an ultrasonic nebuliser and 2-min tidal breathing method. The increase in histamine solution tonicity decreased the histamine PC20 values only in the steroid-naive asthmatic subjects (1.1 (0.5-2.7) vs. 0.5 (0.2-1.2) mg/ml, P = 0.047). Using 1mg/ml as the cut-off value, the sensitivity, specificity, and accuracy of the hypertonic histamine challenge to detect steroid-naive asthma was 81%, 100%, and 90%. The respective values for the isotonic histamine challenge were 56%, 100%, and 77%. Furthermore, there was a statistically significant difference in the hypertonic histamine PC20 between steroid-naive and steroid-treated asthmatic subjects, which could not be detected in the isotonic histamine PC20. The hypertonic histamine PC20 was highly repeatable, with a single determination 95% range of +/-1.35 doubling concentrations. The hypertonic histamine challenge was safe but provoked more cough and throat irritation than the other two challenges. In conclusion, compared with a conventional, isotonic histamine challenge, hypertonic histamine challenge may be more accurate in the diagnosis of asthma and also, more capable to detect the effects of inhaled corticosteroid treatment.

Roken en astma

Asthma is a frequently occurring disease with an increasing prevalence worldwide, that is the highest in childhood. Smoking, both active and passive, is also a widespread problem. Epidemiological and experimental studies show that active and passive smoking have an important influence on the severity and the development of asthma. There is sufficient evidence to conclude that there is a relationship between passive smoking and both the exacerbation and the development of asthma in children. In adults, there is sufficient evidence for a relationship between passive smoking and the exacerbation of asthma, but there is only suggestive evidence for the relationship between passive smoking and the development of asthma. There is sufficient evidence for a relationship between active smoking and the exacerbation of asthma in anybody who smokes. Besides, active smoking impairs the efficacy of inhaled corticosteroid treatment in asthma. There is no evidence for a causal relationship between active smoking and the development of asthma. Children of mothers who smoked during pregnancy or young children who are exposed to environmental tobacco smoke, are at the highest risk to develop asthma during their life. Consequently, every physician plays an important role in helping pregnant women, parents of young children and asthmatic patients (and as a matter of fact every smoker) to stop smoking.

Inhaled Corticosteroids, Corticosteroid Osteoporosis, and the Risk of Fracture in Chronic Asthma

Current guidelines for the diagnosis and treatment of osteoporosis do not address the risks to bone density and the likelihood of fracture that may be associated with inhaled corticosteroid treatment for asthma. This review outlines an approach to the use of bone densitometry in clinical practice for the diagnosis, prevention, and treatment of osteoporosis in asthmatic patients receiving inhaled corticosteroid therapy.

Molecular mechanisms of corticosteroids in allergic diseases.

Molecular mechanisms of corticosteroids in allergic diseases.

Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma

Background: Bronchial asthma is characterized by airway wall remodeling. Matrix metalloproteinases (MMPs) are members of a family of proteolytic enzymes that degrade the extracellular matrix and that restrain the effects of their tissue inhibitors (TIMPs). Treatment with inhaled corticosteroids may prevent airway remodeling in asthma. However, the effects of corticosteroid treatment on MMPs and TIMPs in asthma are unknown. Objective: We examined the effects of inhaled beclomethasone dipropionate (BDP) on the expression of MMP-9 and TIMP-1 and subepithelial collagen deposition in bronchial biopsy specimens from 30 subjects with asthma. Methods: Inhaled BDP, 800 μg daily, or placebo was administered for 6 months in a double-blind, parallel-group study, and bronchial biopsies were performed before and after treatment. Biopsy specimens were examined for extent of collagen type III in the subepithelial basement membrane by means of immunohistochemistry, and expression of both epithelial and submucosal MMP-9 and TIMP-1 was quantitated. Numbers of inflammatory cells were also determined. Results: We observed significant decreases in collagen type III deposition ( P < .01) and the expression of submucosal MMP-9 ( P < .01) and a significant increase in the expression of submucosal TIMP-1 ( P < .05) in the BDP group. Significant correlations were found between the subepithelial collagen type III deposition and epithelial ( r s = 0.37, P < .05) and submucosal expression of MMP-9 ( r s = 0.47, P < .01). Additionally, the number of many inflammatory cells and myofibroblasts in airway mucosa were significantly decreased in the BDP group. Conclusion: Our findings suggest that corticosteroid treatment of asthma can reduce subepithelial collagen deposition by downregulation of MMP-9 expression and upregulation of TIMP-1 expression. (J Allergy Clin Immunol 1999;104:356-63.)

Early or Delayed Corticosteroids For Treatment of Asthma?

Early or Delayed Corticosteroids For Treatment of Asthma?

Lipoprotein levels in elderly patients with asthma

Lipoprotein levels in elderly patients with asthma

Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma. A randomized controlled trial. Zileuton Clinical Trial Group

To study the effect of 3 months of treatment with zileuton, an inhibitor of the enzymatic pathway (5-lipoxygenase) leading to leukotriene formation, on disease control in patients with mild to moderate asthma. Randomized, double-blind, parallel-group study in 401 patients. A 10-day placebo lead-in was followed by a double-blind treatment period of 13 weeks. Asthma study clinics in university hospitals and private practices. Patients with mild to moderate asthma (forced expiratory volume in the first second [FEV1], 40% to 80% of predicted) whose only treatment was inhaled beta-agonists. Treatment with 600 mg or 400 mg of zileuton or placebo (each taken four times daily.) Frequency of asthma exacerbation requiring treatment with corticosteroids, use of inhaled beta-agonists, pulmonary function tests, asthma symptom assessment, and quality-of-life evaluation. Safety was evaluated by monitoring adverse events. Only eight (6.1%) of 132 patients receiving 600 mg of zileuton four times a day required corticosteroid treatment for asthma vs 21 (15.6%) of 135 patients receiving placebo (P=.02), giving a relative risk of 2.6. At the time of expected peak drug concentration, the average FEV1 improved 15.7% in the 600-mg zileuton group vs 7.7% in the placebo group (P=.006). Quality-of-life assessments significantly improved in the 600-mg zileuton group and not in the placebo group (P=.007 for the overall score). Elevations in liver function tests (more than three times normal), all of which reversed with drug withdrawal, occurred in five patients (P=.03 vs placebo), three patients (P=.12 vs placebo), and no patients treated with 600 mg of zileuton, 400 mg of zileuton, or placebo, respectively. Three months of 5-lipoxygenase inhibition produced a significant improvement in asthma control. These data indicate that 5-lipoxygenase products of arachidonic acid metabolism are mediators of inflammation with an important role in the biology of asthma.

Inhaled corticosteroid treatment for asthma.

Increased numbers of goblet cells associated with decrease in the ciliated epithelium occur at an early stage in the patient with asthma. Recent bronchial biopsy studies have demonstrated that these changes may occur even in the mildest asthmatic patient. The protective function of the epithelium is thus compromised and secretion enhanced in early asthma. Anti-inflammatory therapy should be employed at an early stage in the asthmatic patient. Avoidance of allergen is also essential if the source of the inflammation is atopic disease. Inhaled corticosteroids not only reduce bronchial hyperresponsitivity, but also improve the diurnal variation that occurs in lung function in the asthmatic patient. Inhaled corticosteroid therapy is associated with the normalization of the ciliated to goblet cell ratio and a reduction in the inflammatory cell infiltrate, including most notably a reduction in eosinophil within the lamina propria and respiratory epithelium. These changes induced by inhaled corticosteroids are not noted when inhaled beta 2-agonists are employed alone as therapy for asthma. The use of inhaled corticosteroids may thus potentially reverse the pathologic changes that occur even in the early asthmatic patient, whereas utilization of inhaled beta 2-agonists failed to improve histologic abnormalities that occur in early asthma.

Association Between Reported Use of Inhaled Triamcinolone and Differential Short-term Responses to Aerosolized Albuterol in Asthmatics in an Emergency Department Setting

Forty-four adult patients with acute asthma were treated with albuterol at a rate of 15 mg/h over 2 h. Analysis of covariance showed a significantly higher baseline adjusted mean for both percent predicted forced expiratory volume in 1 s (PFEV1) (p = 0.045) and percent predicted forced vital capacity (PFVC) (p = 0.022) at 50 and 110 min for the patients who reported triamcinolone use. Although heart rates decreased overall during the first hour of albuterol treatment, a rise in mean heart rate occurred during the second hour of treatment only in patients reporting triamcinolone use (p = 0.005). After accounting for the effects of parenteral corticosteroids, the effect of reported triamcinolone use remained significant. These data suggest that use of inhaled corticosteroids in this context may be associated with enhanced local and systemic beta-responsiveness, and if a causal relationship could be confirmed, this may constitute yet another advantage of early inhaled corticosteroid treatment in asthma. These data also suggest that chronotropic effects of high-dose albuterol should be monitored in patients using inhaled triamcinolone.

Effect of corticosteroid treatment on interleukin-1 and tumour necrosis factor secretion by monocytes from subjects with asthma.

Peripheral blood monocytes (PBM) may be activated in asthmatic patients, a condition usually reverted by corticosteroid (CS) treatment. In the present research we have evaluated the spontaneous or lipopolysaccharide (LPS)-induced production of interleukin 1 (IL-1) and tumour necrosis factor (TNF) by PBM obtained from 14 asthmatic subjects during an asthmatic attack and after 1 week of CS treatment. The control group included 20 healthy volunteers. PBM obtained during severe asthma showed a pattern of IL-1 and TNF secretion similar to that of normal subjects. After CS treatment, IL-1 levels did not change significantly in comparison to baseline values, while LPS-induced TNF production was apparently related to the degree of airway obstruction after CS treatment. In fact, TNF production by PBM from CS-responsive subjects was significantly decreased in comparison to the levels determined before CS treatment, while PBM from CS-resistant subjects produced the same cytokine levels regardless of CS treatment. The present study suggests that the determination of LPS-induced TNF secretion by PBM could be used to confirm the effectiveness of CS treatment in asthma.