We evaluated the use of sputum neutrophils and IL-8 as predictors for the development of asthma exacerbations. Our study indicates that neutrophils, rather than eosinophils, are associated with asthma exacerbations following steroid withdrawal. This may result from the increase in sputum IL-8 observed prior to the onset of an exacerbation. Taken together, our findings demonstrated that sequential monitoring of sputum IL-8 and neutrophils might be useful for predicting an episode of severe exacerbation in moderate persistent asthma after corticosteroid withdrawal. This study also confirms that the mechanisms underlying asthma exacerbation are highly variable.
There is growing evidence that reducing asthma exacerbations is achieved by targeting therapy to eosinophilic inflammation. An eosinophilic exacerbation is triggered by allergen exposure. However, several studies, have demonstrated increased neutrophil numbers in airway secretions and airway tissue from patients with acute severe asthma treated with ventolin effectively. Sputum neutrophilia may be mediated by IL-8, a che-mokine that selectively attracts neutrophils. IL-8 is increased in sputum of asthmatic subjects during exacerbations in association with sputum neutrophil-ia. However, there is no clear relationship between the type of airway inflammation and asthmatic exacerbations, possibly due to differences in the methodology, specifically the use of steroid tapering. Furthermore, the pathophysiologic mechanisms underlying asthma exacerbations following abrupt steroid withdrawal in moderate persistent asthmatics may be distinct from those seen with gradual steroid tapering. The neutrophilic airway inflammation in the present study may reflect the sudden withdrawal of inhaled corticosteroids and reflect the kinetics of inflammatory cells in an acute exacerbation when neutrophils are the first cells to infiltrate the airways.
Patient characteristics are shown in Table 1. Two patients in the budesonide treatment group were excluded from the analysis: one was unable to attend for all of the study visits, and the other provided induced-sputum specimens containing squamous cell counts > 80%.
Eight of 12 patients had an exacerbation over the 10-week period of steroid withdrawal (Table 3). The remaining four subjects did not have an exacerbation during the 10 weeks of follow-up. Only 1 of 10 patients in the budesonide treatment group had an asthma exacerbation at week 2 (Table 2). Buy ventolin, flovent or advair to treat asthma effectively.
Twenty-four nonsmoking patients (10 men) with moderate, persistent asthma participated in the study. The inclusion criteria were age 18 to 60 years of age and a history of stable asthma as defined by the American Thoracic Society. Patient characteristics are summarized in Table 1. All patients had a baseline FEVj > 70% of predicted, FEV1 reversibility > 15%, and required regular treatment with moderate doses of inhaled corticosteroids (beclomethasone dipropionate, 800 ^g/d or equivalent) for > 3 months. All patients were hyperresponsive as measured by a provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) < 8 mg/mL. None of the patients had a history of respiratory disease other than asthma, and none required oral glucocorticoid treatment within 3 months before study entry and used any other medication except study medication during the trial. The patients were included during a clinically well-controlled period without symptoms of an upper respiratory tract infection for 4 weeks prior to the study. The study was approved by the Royal Brompton and Harefield NHS Hospital Trust Ethics Committee, and informed consent was given by all patients. All patients suffering from asthma may order asthma inhalers online to treat asthma attacks.
Although eosinophilic airway inflammation is recognized as an important feature of some patients with chronic, stable asthma, evidence supports an important role of neutrophils in acute exacerbations. In stable asthma, there is typically an infiltrate of eosinophils, which occurs in response to cytokines such as interleukin (IL)-5, secreted by
T-helper type 2 lymphocytes. In contrast, during acute exacerbations of asthma, the airway inflammatory response is both more intense and heterogeneous. The increased intensity of airway inflammation is reflected by an elevated total cell count in sputum. The heterogeneity of the inflammatory response is reflected by an increase in neutrophils as well as eosinophils, and there are reports of exacerbations without sputum eosinophilia. There is also evidence for increased expression of the potent neutrophil chemoattractant IL-8, in addition to the presence of IL-5. There is heterogeneity in the concentrations of IL-8 in patients with moderate asthma and the strong correlation between the concentration of IL-8 release by peripheral blood mononuclear cells and the frequency of asthma exacerbations. Buy asthma inhalers online to arrest asthma attacks (read about Ventolin and Flovent) .
The hypothesis of Szentivanyi that bronchial asthma is associated with impaired 0-adrenoceptor function has been tested in several investigations in recent years. Most of these studies have been performed on leukocytes from peripheral blood, since these cells are easily accessible and since they are endowed with 0-adrenoceptors of the 02-subtype, as is human lung tissue. The interpretation of results from some of these studies is confounded by the findings that the (3-adrenoceptors of white blood cells are down-regulated by antiasthmatic therapy with β-adrenoceptor agonists. Such down-regulation of 0-adrenoceptors in white blood cells disappears within one week after discontinuation of treatment.
Twelve subjects were studied. All were wheezing at the time of study and all had moderate-to-severe airways obstruction with an FEV! between 720 ml and 1,500 ml. Table 1 shows the FEV, on pulmonary function tests done before and after bronchodilators, performed within four weeks of the lung sound recording.
In Europe, as on other continents, bronchial asthma is a common disorder with widely variable clinical features. It is frequently not diagnosed and, if diagnosed, its severity is often underestimated by the medical profession as well as by patients and their families. Failure to diagnose or to correctly estimate the severity leads to considerable undertreatment. Moreover, in few other chronic conditions have more divergent opinions been noted concerning the correct type and order of treatment to be applied to the chronic state of the disease, as well as to its acute exacerbations. This was also brought out by a pilot survey conducted on the basis of a questionnaire among 68 chest physicians from seven European countries during the summer of 1983; although clear patterns of responses emerged among the physicians of each country, there was considerable disagreement among countries on the proper choice and dosage of drugs and ventolin inhalers for asthma therapy. Because of the interest generated by the presentation and the discussion of this survey at the Second Annual Meeting of the European Society of Pneumology in Edinburgh, it was decided to enlarge the scope into a complete European Audit on Diagnosis and Treatment of Asthma, covering all major countries of western Europe and using an improved and extended questionnaire.
The prevalence of asthma and allergic disease has increased substantially during recent decades, and to a large extent the causes for this increase are still imperfectly understood. It is well recognized that the incidence of asthma is greater in childhood compared to adulthood, and that the male subject/ female subject ratio of incident asthma diminishes with increasing age. However, an interest in adult-onset asthma has emerged, not in the least due to reports coming from several large-scale longitudinal studies from Europe (European Community Respiratory Health Survey2) and the and United States (National Health and Nutrition Examination Study), pointing out the growing impact of adult respiratory allergic disease morbidity. No single hypothesis can explain this widened distribution of disease, but a biologically plausible model is likely to include environmental risk factors associated with a westernized lifestyle interacting with individual susceptibility genotypes. In a search for factors fitting such a model, several environmental determinants have been shown be part of the cause of adult-onset wheezing illness, including female sex, upper airway allergic disease, sensitization to aeroallergens,> obesity, exposures encountered at work, and perhaps hormone replacement therapy. Still, longitudinal data on incident asthma among adults are sparse, and the study of these data may therefore provide new insight into the development and natural history of the disease.
Effects of Mometasone Furoate Dry Powder Inhaler and Beclomethasone Dipropionate Hydrofluoroalkane and Chlorofluorocarbon: Discussion
This study compared the effect of MF-DPI on the HPA axis with that of another commonly used ICS, BDP, in subjects with asthma. The results demonstrate that a similar magnitude of HPA-axis suppression occurred with BDP via HFA and CFC MDI, despite the differences in BDP doses: 200 ^g bid vs 400 ^g bid. This confirms previous findings by Jackson and Lipworth- indicating greater systemic bioavailability and enhanced cortisol suppression with the HFA formulation of BDP vs the CFC formulation. The median percentage reduction in the serum cortisol concentrations AUC0-24 of 23 to 24% with BDP was significantly greater than the 9% reduction seen with MF-DPI treatment. This low magnitude of cortisol secretory suppression seen with MF-DPI is in keeping with a previous 28-day study in subjects with mild-to-moderate asthma. In that study, MF-DPI at doses from 200 ^g bid to 1,200 ^g qd had no impact on dynamic cortisol secretion in response to low-dose cosyntropin, while the mean serum cortisol concentrations AUC0-24h was in the range of 82 to 107% of placebo.
The minor effect of MF-DPI treatment on serum cortisol concentrations AUC0-24h compared with BDP in the current study was reflected in the results of the 24-h UFC excretion. The mean decrease in 24-h UFC excretion of 9.6% ( — 8.2 nmol/L/24 h) with MF-DPI was lower than the decreases seen with HFA-BDP (34.3%; — 27.9 nmol/L/24 h; p = 0.047) and CFC-BDP (33.4%; — 18.0 nmol/ L/24 h; p = 0.073). The difference between the MF-DPI and BDP groups was maintained in the subpopulation with validated full 24-h urine samples (MF-DPI, — 9.6% [— 5.9 nmol/L/24 h]; HFA-BDP, — 43.1% [— 34.8 nmol/L/24 h]; and CFC-BDP, — 30.0% [— 19.1 nmol/L/24 h]). Subjects in the MF-DPI group had greater improvements from baseline in PEF measured morning (35 L/min) and evening (41 L/min), compared with BDP (morning, 20 to 21 L/min; evening, 17 L/min; p = not significant).
Roles of Angiopoietin-1 and Angiopoietin-2 on Airway Microvascular Permeability in Asthmatic Patients: Methods and Materials
Thirty patients with asthma and 12 age-matched control subjects were included in the study. All control subjects were healthy, nonsmoking volunteers who had no history of lung disease. All patients with asthma were recruited from respiratory outpatient clinics at our institution; they were nonsmokers and satisfied American Thoracic Society criteria for asthma. Methacholine inhalation challenge testing was performed for all study subjects as we previously described. All subjects with asthma in this study demonstrated bronchial hyperreactivity to methacholine. Exhaled nitric oxide (NO) was measured for all subjects with a chemiluminescence analyzer (CLM-500; Shimazu; Kyoto, Japan) in accordance with American Thoracic Society standards. The mean value of three expiratory NO concentrations was calculated for each subject and expressed as parts per billion. At study entry, regular medication in asthmatic patients consisted of short-acting p2-agonists on demand. No patients were receiving oral or inhaled corticosteroids. All patients with asthma were clinically stable, and none had a history of respiratory infection for at least the 4-week period preceding the study. All subjects gave their written informed consent for participation in the study, which was approved by the ethics committee of Osaka City University.