Severe Steroid-dependent Asthma Research Articles

Severe asthma phenotypes in patients controlled with omalizumab: A real-world study.

The appropriate identification of asthma phenotypes of responders to omalizumab would optimize the selection of treatment. To describe the most frequent clinical phenotypes in patients with severe asthma responding to omalizumab and their clinical and pulmonary function improvement. This was an observational, retrospective, multicenter study. Adult patients with severe asthma, who achieved good control after the first year of treatment with omalizumab were included. Omalizumab was prescribed according to clinical routine practice. Responders were assigned to one pre-established phenotype based on the most predominant one before they had started treatment with omalizumab, all according to the physician's criteria. Data about asthma symptoms, number of non-severe asthma exacerbations, medication intake (inhaled and oral corticosteroids and rescue medication), lung function, high fractional exhaled nitric oxide (FeNO) and peripheral eosinophils counts were recorded. Among the 345 patients included, the main phenotypes were severe asthma with frequent exacerbations (29.9%), early-onset allergic asthma (23.8%), severe steroid-dependent asthma (18.8%), and severe eosinophilic asthma (13.6%). Clinical and respiratory changes observed after first year of treatment with omalizumab included: reduction in asthma symptoms, reduction in the use and dose of corticosteroids and need for rescue therapy, improvement of pulmonary function, reduction in the number of episodes of non-severe asthma exacerbations regardless of the duration of severe disease since the diagnosis. Increased blood levels of peripheral eosinophils and high FeNO levels were found at baseline. Several heterogeneous severe asthma phenotypes were observed as good responders to omalizumab.

Risk factors associated with severe asthma exacerbations in children attending Alexandria University Children’s Hospital, Egypt

Background: Severe asthma exacerbation is one of the common pediatric medical emergencies that necessitates hospital visits. The study aimed to identify risk factors associated with pediatric severe asthma exacerbations that might have the potential to guide the parents for early medical consultations and physicians at primary health care centers for proper management.Methods: A case-control study was conducted on over 100 asthmatic children below 12 years attending the Emergency Department of Alexandria University Children’s Hospital in acute exacerbation. Based on a modified pulmonary index score, the patients were allocated into 2 groups; study group (50 patients with severe asthma exacerbation) and control group (50 patients with mild asthma exacerbations). Demographic data, history of illness, alarming clinical signs, medications, and outcome of all participants were recorded.Results: Severe asthma exacerbations were more encountered among males, older age, and with a longer duration of asthma (X±SD=28.4±15.9 months) with significant differences when compared to controls. Comparing the studied groups revealed higher risk for severe asthma exacerbations mainly with; history of sudden onset of severe respiratory distress (Odds ratio “OR”=30.13, 95% CI, 13.78-66.69) and chronic steroid-dependent asthma (OR=14.46, 95% CI, 3.97-52.65). Cyanosis, lethargy, and inability to talk were alarming signs in patients with severe asthma exacerbation when compared to those with mild asthma exacerbation (p<0.05).Conclusions: Severe asthma exacerbation in children is still associated with many risk factors that may alert the patients’ caregivers and physicians prospectively for early proper management.

Aspirin Desensitization Treatment for the Management of Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to cyclooxygenase-1 (COX-1) inhibitors. The treatment of asthma and chronic rhinosinusitis in AERD is difficult, since those patients usually suffer from severe steroid dependent asthma and frequent recurrence of nasal polyps despite combined medical and surgical treatment. Aspirin desensitization (AD) can be considered as an additional treatment option in selected patients with AERD. Aspirin doses ranging from 100 to 1300 mg/day were reported to be effective for this purpose.

The effects of laparoscopic Nissen fundoplication on patients with severe gastroesophageal reflux disease and steroid-dependent asthma

BackgroundAn association between severe reactive airway disease (RAD) and gastroesophageal reflux disease (GERD) in children has been previously noted, but the relationship has not been well characterized. This study reports our experience with laparoscopic Nissen fundoplication and its effect on the pulmonary status of children with severe steroid-dependent RAD. MethodsBetween January 1993 and June 2011, 235 patients with severe steroid-dependent RAD and medically refractory GERD underwent laparoscopic Nissen fundoplication. Clinical response, ability to wean oral and inhaled steroids, and changes in pulmonary function testing were tracked during the postoperative period. ResultsOf 235 patients, 215 (91%) noted significant subjective improvement in their respiratory symptoms by the first postoperative visit at 2 weeks. Eighty percent was successfully weaned off their oral steroids within the first 2 postoperative months. Ninety-five percent reported a decrease in their inhaler use. Twenty-four percent of patients studied had a documented increase in their forced expiratory volume in the initial postoperative period. There were no intraoperative complications and no postoperative respiratory tract infections. ConclusionChildren with steroid-dependent RAD and documented GERD refractory to medical management show improvement in their respiratory status after laparoscopic Nissen fundoplication. Many can be weaned off of their oral and inhaled steroids postoperatively.

Refractory Asthma : An Overview

Patients whose asthma is not adequately controlled despite treatment pose a major clinical challenge and it is an important health care problem. It carries several names; each one points to an aspect of the disease. Chronic severe asthma, steroid-dependent asthma, steroid-resistant asthma, difficult-to-control asthma and refractory asthma are some of these terminologies. Patients with severe refractory disease often require regular oral corticosteroid with an increased risk of steroid-related adverse events. Alternatively, immunomodulatory and biologic therapies may be considered, but they show wide variation in efficacy across studies, thus limiting their generalization. Managing asthma that is refractory to standard treatment requires a systematic approach to evaluate adherence, ensure a correct diagnosis, identify coexisting disorders and trigger factors. In future phenotyping of patients with severe refractory asthma will also become an important element of this systematic approach.
 TAJ 2011; 24(1): 57-61

Cytokines or Their Antagonists for the Treatment of Asthma

T helper (Th) type 2 cytokines, particularly interleukin (IL)-4, IL-5, and IL-13, may be important in the development of allergic asthma. Humanized monoclonal antibodies (MoAbs) against IL-5 and a recombinant human soluble IL-4 receptor (sIL-4R) have been developed as possible treatments. These approaches have not yet proven to be successful in patients with persistent asthma. This may suggest that neither IL-4 nor IL-5 is important in asthma pathogenesis. There is, however, insufficient information about the efficacy of sIL-4R and the anti-IL-5 MoAbs in asthma to draw any firm conclusions about the importance of these Th2 cytokines. Also, the administration of the potentially antiinflammatory cytokines IL-12 and interferon-gamma has not shown benefit in asthmatic patients. By contrast, the treatment of severe oral steroid-dependent asthma with soluble tumor necrosis factor-alpha receptor has demonstrated very promising results, suggesting that this cytokine plays an important role in the persistence of severe asthma.

0023—Growth Hormone Treatment of a Child with Growth Hormone Deficiency, Type I Diabetes, and Chronic Steroid Use

P.K. is 14 years 4 months old, has had severe steroid-dependent asthma since infancy, and was diagnosed with type I diabetes at the age of 3 years. He has been hospitalized numerous times for his asthma, or diabetes, or both conditions. A review of our hospital records notes at least 35 admissions (not counting ER visits) in the past 4 years, with at least one to two intensive care unit interventions yearly. His growth has been consistently under the 5th percentile since he was 5 years old, which is attributed to his suboptimal diabetes control (glycosylated hemoglobin [HgA1C], 8.5–9%; normal, <5.8%) and frequent high-dose prednisone therapy administered orally. In 2000, his short stature became a major issue with P.K. and his family, and they requested a workup and possible therapy. Growth hormone (GH) testing was delayed because of numerous hospitalizations, but it was completed in 2005. He is GH-deficient and recently started GH therapy.

Blood neutrophil activation markers in severe asthma: lack of inhibition by prednisolone therapy

BackgroundNeutrophils are increased in the airways and in induced sputum of severe asthma patients. We determined the expression of activation markers from circulating neutrophils in severe asthma, and their supressibility by corticosteroids.MethodsWe compared blood neutrophils from mild, moderate-to-severe and severe steroid-dependent asthma, and non-asthmatics (n = 10 each). We examined the effect of adding or increasing oral prednisolone (30 mg/day;1 week).ResultsFlow cytometric expression of CD35 and CD11b, but not of CD62L or CD18, was increased in severe asthma. F-met-leu-phe increased CD11b, CD35 and CD18 and decreased CD62L expression in all groups, with a greater CD35 increase in severe asthma. In severe steroid-dependent asthma, an increase in prednisolone dose had no effect on neutrophil markers particularly CD62L, but reduced CD11b and CD62L on eosinophils. Phorbol myristate acetate-stimulated oxidative burst and IL-8 release by IL-1β, lipopolysaccharide and GM-CSF in whole blood from mild but not severe asthmatics were inhibited after prednisolone. There were no differences in myeloperoxidase or neutrophil elastase release from purified neutrophils.ConclusionBecause blood neutrophils in severe asthma are activated and are not inhibited by oral corticosteroids, they may be important in the pathogenesis of severe asthma.

Symbicort in steroid-dependent asthma: reduction of oral steroids requirements

Objective: to study the ability of inhaled Symbicort to reduce daily oral steroids (OS) requirements in patients with severe steroid-dependent asthma. Methods: 16 patients with severe steroid-dependent asthma were included into the study (5 males, 11 females, mean age 53 ± 8 years, mean dose of OS 10.9 ± 5.2 mg / day, mean OS treatment duration 9.3 ± 4.1 years, mean FEV1 59.3 ± 15.1%). All patients received Symbicort administered by means of a multidose poder inhaler 4.5 / 160 mkg 2 inhalations twice daily, every 2 weeks patients underwent controlled OS reduction on the basis of predetermined asthma stability criteria. Results: OS was eliminated or reduced in 14 patients (87.5 %), the OS dose was reduced to 3.3 ± 6.8 mg / day (р &lt; 0.001). At the end of 12 weeks of Symbicort therapy FEV1 and FVC increased by 18.6 % and 8.9 %, respectively. Daytime and nighttime asthma symptom severity scores improved in average by 1 point (р &lt; 0.001). The number of inhalations of short-acting β2-agonists reduced from 3.4 ± 1.7 to 1.5 ± 1.3 puffs / day (р &lt; 0.001). Statistically and clinically significant improvements were seen in all 4 domains of quality of life scores (AQLQ) (р &lt; 0.001). The level of NOex reduced significantly form 18.6 ± 11.4 ppb at baseline to 7.9 ± 2.8 ppb after 12 weeks (р = 0.001). The side effects of OS were reduced to the end of study. Conclusion: in patients with severe steroid-dependent asthma therapy with Symbicort allows to eliminate or reduce OS therapy with improved lung function, improved daytime and nighttime asthma symptoms, improved asthma-specific quality of life, reduction of short-acting β2-agonists use and reduction of side effects of OS.

Role of intravenous immunoglobulin in severe steroid-dependent asthma.

Subgroups of asthma patients have extremely severe respiratory symptoms that require chronic use of steroids for disease control. These patients are at risk of significant side-effects from chronic exposure to high doses of oral steroids. Intravenous immunoglobulin (IVIG) has immunomodulatory properties as shown by its use in some immune disorders. A few trials have suggested a possible benefit in individuals with severe asthma. To evaluate the role of IVIG as an adjunctive therapy in steroid-dependent asthma, monitoring the outcomes of lung function and measured reduction in oral steroid requirement. Seven patients with severe steroid-dependent asthma were given IVIG at a dose of 1 g/kg each month for 6 months. Baseline pulmonary function tests and immunoglobulin levels were obtained. At the end of 6 months, the end-points observed were lung function and the degree of reduction in the dose of oral steroids. The number of hospital admissions during the 12 months following commencement of IVIG was compared with the preceding 12 months. There was a significant reduction in daily prednisolone dose from 56 +/- 31 mg to 39 +/- 35 mg (P=0.04, Wilcoxon rank sum test) and a decrease in the number of hospital admissions from 5.9 +/- 2.9 to 3.6 +/- 3.5 (P=0.04). No significant improvement occurred in lung function. IVIG provides a potentially important adjunctive therapy in severe steroid-dependent asthma, reducing steroid requirement and decreasing hospital admissions, but not improving lung function.

Significant improvement in an adolescent with severe steroid-dependent asthma following clarithromycin therapy

Significant improvement in an adolescent with severe steroid-dependent asthma following clarithromycin therapy

Infliximab therapy for severe steroid-dependent asthma and COPD: A case report

Infliximab therapy for severe steroid-dependent asthma and COPD: A case report

Open-Label Trial of High-Dose Intravenous Immunoglobulin in Patients with Severe Asthma

Anti-inflammatory corticosteroid therapy is highly effective, however, the long term adverse effects may be devastating for patients with severe asthma. Intravenous immunoglobulin (IVIG) is known to have immunomodulatory effects, and in a few clinical trials has been shown to have potential benefit as a steroid-sparing agent in asthma patients requiring high doses of corticosteroids. This study assessed the efficacy of high-dose IVIG in reducing the steroid requirement and subsequently improving the pulmonary function, symptomatology, and quality of life in patients with severe steroid-dependent asthma. Six immunocompetent, steroid-dependent patients were enrolled in an open-label trial of IVIG given as six monthly infusions of 2 g/kg per dose. Five patients completed the study. Of these, four showed a significant reduction in oral corticosteroid requirement while being treated with IVIG. The mean reduction was 10.1 mg/d (p = 0.02), which was an almost 50% decrease in corticosteroid requirement. Two patie...

Inhibitory effect of lidocaine on T cells from patients with allergic asthma

Background: Nebulized lidocaine enables dosages of oral corticosteroids to be tapered in the treatment of severe asthma. Objective: We sought to investigate the effect of lidocaine on T cells from patients with allergic asthma. Methods: PBMCs and CD4 + T cells were isolated from 6 patients with asthma and house dust mite allergy. PBMCs were cultured with lidocaine for up to 7 days and then stained with propidium iodide to evaluate the involvement of apoptosis. In addition, the viability of CD4 + T cells when cultured with lidocaine was investigated. Effects of lidocaine on proliferative response, mRNA expression, and protein production of IL-5 and IFN-γ by PBMCs were investigated after stimulation with Dermatophagoides farinae, purified protein derivative, and phorbol 12-myristate 13-acetate plus calcium ionophore. The effects of lidocaine on the proliferative response of steroid-insensitive PBMCs from 6 nonallergic donors induced by preculture with IL-2 and IL-4 were also investigated. Results: No significant increase in the staining of PBMCs with propidium iodide was observed in the presence of 100 μmol/L lidocaine. The viability of CD4 + T cells was not significantly affected by culture with lidocaine at this concentration. However, lidocaine inhibited, in a dose-dependent manner, the proliferative response and mRNA expression and protein production of IL-5 and IFN-γ of PBMCs stimulated with D farinae, purified protein derivatives, or phorbol 12-myristate 13-acetate plus calcium ionophore. Preincubation of PBMCs with IL-2 and IL-4 significantly decreased the inhibitory effects of both corticosteroids and lidocaine compared with that after preincubation with medium alone. Conclusion: Lidocaine has immunoregulatory effects on T cells. Therefore, lidocaine might be studied as an anti-inflammatory agent in the treatment of severe steroid-dependent asthma. (J Allergy Clin Immunol 2002;109:485-90.)

The Editors' Choice

The Editors' Choice

Corticosteroids, IgE, and atopy.

Corticosteroids, IgE, and atopy.

Rhinosinusitis in severe asthma

Background: Chronic rhinosinusitis is a common comorbidity of asthma. However, sinonasal involvement in severe steroid-dependent asthma is still undefined. Objective: The aim of the study was to evaluate chronic rhinosinusitis in 35 patients with severe steroid-dependent asthma by using a clinical score and coronal computed tomography (CT) scanning. Methods: Thirty-five subjects (16 female subjects) with severe asthma requiring daily doses of oral corticosteroids were compared with 34 patients (19 female patients) with mild-to-moderate asthma. Sinonasal involvement was studied by using clinical and CT scores. Airflow obstruction, therapy requirement, and asthma triggering factors were carefully assessed. Results: The proportion of patients with symptoms of rhinosinusitis was similar in both groups of asthmatic subjects (74% in patients with severe steroid-dependent asthma and 70% in patients with mild-to-moderate asthma). All subjects with steroid-dependent asthma versus 88% of subjects with mild-to-moderate asthma had abnormal CT scan results. The clinical (P < .05) and CT scan (P < .0005) severity scores were higher in the subjects with severe steroid-dependent asthma. In both groups the CT scan scores were correlated to the clinical scores (P < .0001 and P < .006), but only in the mild-to-moderate group were both scores correlated with high significance (P < .002 and P < .0005) to the absolute number of blood eosinophils. Conclusion: Frequency of rhinosinusitis in patients with mild-to-moderate or severe steroid-dependent asthma is similar; however, sinonasal involvement, as evaluated by clinical symptoms and CT scan imaging, is significantly greater in the patients with severe steroid-dependent asthma than in those with mild-to-moderate asthma. (J Allergy Clin Immunol 2001;107:73-80.)

Oral-steroid sparing effect of inhaled fluticasone propionate in children with steroid-dependent asthma

To evaluate the oral steroid-sparing effect of inhaled fluticasone propionate (FP) in eight children with steroid-dependent asthma. Treatment protocol study at a tertiary pulmonary care centre at a children's hospital. Eight children with severe persistent steroid dependent asthma (mean age 11.6 years [range 10 to 13 years], mean duration of asthma 8.37 years [range three to 11 years]) were enrolled in the study. Inhaled FP 880 mug/day (two puffs of 220 mug/puff, two times a day) was added to the children's asthma treatment, and attempts were made to reduce the dose of oral steroids by 20% every two weeks over a six-month period. After this six-month period, in the patients responding to inhaled FP, the dose of inhaled FP was reduced to 440 mug/day (two puffs of 110 mug/puff, two times a day) for the next six months. The mean percentage predicted values for forced expiratory volume in 1 s (FEV(1)) and maximal mid-expiratory flow rate (FEF(25%-75%)) were compared during the first month, at two to six months, and at seven to 12 month intervals before and after starting FP. The number of asthma exacerbations, emergency room visits, hospital admissions and number of school days lost were also compared. Within three months of starting inhaled FP, the mean alternate-day oral steroid dose decreased from 38 mg to 2.5 mg. In addition, six patients (66%) were able to discontinue the use of oral steroids. There was significant improvement in the number of mean emergency room visits per patient (P=0.016), mean asthma exacerbations per patient (P=0.016), mean hospital admissions per patient (P=0.016) and mean number of school days lost per patient (P=0.004) while patients were receiving high dose inhaled FP compared with oral steroids. There was no deterioration of any of the above mentioned parameters during the six month period when the dose of inhaled FP was reduced. The mean FEV(1) and FEF(25%-75%) during the two- to six-month and seven- to 12-month periods showed significant improvement, while the patients were receiving FP compared with oral steroids (P<0.05 for both parameters for both time periods). High dose inhaled FP 880 mug/day has an important oral steroid-sparing effect. After oral steroids are tapered, patients maintain adequate control of asthma with low dose inhaled FP. These findings suggest that FP may control asthma better than oral steroids.

Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy

Background: Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. Objective: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects. Methods: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic. Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma. Prednisone (40 mg/1.73 m 2) and methylprednisolone (40 mg/1.73 m 2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course. Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy. Results: Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations. Conclusions: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects. Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma. To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy. (J Allergy Clin Immunol 1999;103:1031-5.)

Nebulized lidocaine in the treatment of severe asthma in children: a pilot study.

Glucocorticoids have been used to treat asthma since the 1950s; however, their adverse systemic effects have limited their duration of use and dosage. Unfortunately, many patients with severe asthma often require oral glucocorticoids in addition to inhaled glucocorticoids. Alternatives to glucocorticoids have been sought with mixed success. Recently, lidocaine has been added to the list of potent glucocorticoid sparing agents for the treatment of severe asthma. We report the first group of pediatric patients with severe asthma treated with nebulized lidocaine. The study was performed in an open manner with 6 severely asthmatic patients followed in the Pediatric Allergy and Immunology Section, Mayo Clinic. The only intervention was the institution of nebulized lidocaine (0.8 mg/kg/dose to 2.5 mg/kg/dose t.i.d to q.i.d). The average daily steroid requirement was followed during the administration of the nebulized lidocaine. During a mean of 11.2 months of therapy (range 7 to 16 months) 5 of the 6 patients completely discontinued their oral glucocorticoids within an average time of 3.4 months (range 1 to 7 months). After further study, lidocaine may prove to be the first non-toxic, steroid alternative to patients with severe steroid-dependent asthma.