Chronic Stable Asthma Research Articles

NEW MEDICATIONS FOR ASTHMA

The therapy for chronic stable asthma and acute asthma exacerbations continues to evolve as the pathogenesis of asthma becomes better understood. Although the role of many standard therapies for asthma is well established, some carry significant side effects. The newer anti-inflammatory medications have demonstrated both therapeutic benefit as well as reassuring safety profiles. The challenge of the future is to incorporate the newer medications described, as well as those still being examined, into a treatment regimen that can deliver maximal therapeutic benefit with the lowest possible incidence of side effects.

Diagnostic accuracy of sputum outcomes in chronic stable asthma

Asthma with non-remitting airflow obstruction may not always be differentiated from COPD with airway hyperreactivity. Many attempts have been made to find useful markers for the distinction between these two disorders. In order to help the finding of a useful marker for the diagnosis of asthma in the population of patients with airway obstruction we analysed the diagnostic accuracy of sputum eosinophils and sputum ECP in 91 patients with asthma, 15 patients with chronic bronchitis, 32 patients with chronic obstructive pulmonary disease (COPD) and 20 controls subjects, by performing ROC analysis. Sputum eosinophils were above the normal range of our laboratory (0-3.7%) in 48 asthma patients and in six COPD patients, while sputum ECP (normal range < 85 microg/L) was high in 65 asthma patients, in 24 COPD patients and in nine chronic bronchitis patients. The ROC analysis revealed that sputum eosinophils count (AUC = 0.82) was more accurate than both sputum ECP levels (AUC = 0.56) (P < 0.0001) and beta2-reversibility (AUC = 0.53) (P = 0.0001) in differentiating asthmatic from non-asthmatic subjects (COPD, chronic bronchitis patients and normal subjects). The diagnostic accuracy of ECP was similar to that of bronchial reversibility (P = 0.76). When ROC analysis was performed by including only patients with airway obstruction (36 asthmatics with airway obstruction and COPD patients), both eosinophil count (AUC = 0.77) and beta2-reversibility (AUC = 0.66) were more accurate than ECP measurement (AUC = 0.39) in discriminating asthmatics from COPD patients (P < 0.00001 and P = 0.04, respectively). Sputum eosinophils seem to be valid markers for detecting asthma in a population of patients with airway obstruction. Moreover, the higher diagnostic accuracy of eosinophils in the sputum compared to sputum ECP and bronchial reversibility reinforces the role of cytological analysis of sputum in the diagnosis of chronic stable bronchial asthma.

Pilot study of a home-based asthma health education program 1,2

Objective: Caring for a child with asthma can affect the parent’s coping and well-being and coping strategies. This study examined the influence of a home-based asthma health education program on parental coping and quality of life. Design: Randomized controlled non-blinded clinical trial. Setting: Northern community pediatrician’s office. Patients: Families whose children, under the age of 11, had chronic stable asthma, and who presented to the pediatrician’s office for continuing care; those with an acute exacerbation of asthma were excluded. Interventions: Families were randomly assigned to receive either a single two-hour, standardized home-based asthma health education session or a booklet representing conventional care. Main Outcome Measures: One and three-months following the intervention, assessments were obtained for coping measured by Hymovich’s Parent Perception Inventory (PPI), quality of life measured by the Pediatric Asthma Caregiver Quality of Life Questionnaire (PACQLQ) and change in asthma measured by the Caregiver Perception of Change (CPC) survey. Results: Forty families were recruited and randomized; baseline characteristics were similar between groups. At the final follow-up, reduction in parental need for asthma information ( p=0.04), reduction in parental concerns ( p=0.02) and increased use of coping strategies ( p=0.04) were observed in the home-based care group. Improvement was noted in the parent’s perception of their child’s asthma in the home-based asthma education group ( p=0.01). Quality of life as measured by the PACQLQ remained unchanged over the intervention period ( p>0.05). Conclusions: These results suggest the use of a one-time, flexible, home-based intervention to assist families caring for children with asthma should be considered and appears effective.

Acute inpatient care of status asthmaticus.

The hospital management of status asthmaticus includes aggressive use of a limited armamentarium of medications. Understanding the appropriate use of available medications is key. Proper assessment of the severity of an acute episode and response to applied therapies is essential for optimum outcomes without undue delays in treatment and excessive costs. Ensuring that all patients discharged from the hospital receive an individualized treatment plan for the management of chronic stable, worsening, and acute asthma can help prevent future hospitalizations.

A review of clinical use of theophylline in acute asthma: factors influencing kinetic disposition and drug interactions.

The clinical use of theophylline as a first line bronchodilator has declined during the last two decades. However, many therapeutic mechanisms for bronchial asthma have been discovered, and recent studies have suggested that theophylline therapy can play a beneficial role in the management of both chronic stable asthma and exacerbated disease treated in the emergency setting. In this article, the author describes the pharmacokinetics of theophylline and the major factors that influence the kinetics of the drug, such as physiopathological conditions and interactions with concomitantly administered drugs. Practical guidelines are then given on how to achieve optimal serum levels when planning theophylline therapy, including use of nomograms to decide loading and maintenance doses for nonsmoking adult asthmatic patients and adjustments for asthmatic patients with complications or on other drugs that may alter the kinetic disposition of theophylline.

Homeopathy for chronic asthma.

Homeopathy involves the use, in dilution, of substances which cause symptoms in their undiluted form. It is one of the most widespread forms of complementary medicines and is also used to treat asthma. The objective of this review was to assess the effects of homeopathy in people with chronic stable asthma. We searched the Cochrane Airways Group trials register, the Cochrane Complementary Medicine Field trials register, the Glasgow Homeopathic Hospital database, the Muenchener Modell database and reference lists of articles. Randomised and possibly randomised trials of homeopathy for the treatment of stable chronic asthma, with observation periods of at least one week. Data extraction was done by one reviewer and checked by the second reviewer. Trial quality was assessed by the reviewers. Three trials with a total of 154 people were included. These trials were all placebo-controlled and double-blind, but of variable quality. They used three different homeopathic treatments which precluded quantitative pooling of results. The standardised treatments in these trials are unlikely to represent common homeopathic practice, where treatment tends to be individualised. In one trial, severity of symptoms was lessened in the homeopathy group compared to the placebo group. In another trial, lung function measures and medication use showed improvement in the homeopathy group compared to the placebo group. The third trial found improvement in both the homeopathy and placebo groups, but no difference between the groups. There is not enough evidence to reliably assess the possible role of homeopathy in asthma. As well as randomised trials, there is a need for observational data to document the different methods of homeopathic prescribing and how patients respond.

Nebulized glucagon in the treatment of bronchospasm in asthmatic patients

This study sought to determine if nebulized glucagon, a well-known smooth muscle relaxant, is effective in relieving asthmatic bronchospasm. Ten subjects, aged 12 to 26 years, with chronic stable asthma were studied in a pulmonary function laboratory under a randomized double-blind, placebo-controlled, crossover design. Bronchospasm was induced in each subject with progressive doses of nebulized methacholine until forced expiratory volume in 1 second (FEV 1) had decreased at least 20% from baseline. Subjects then received either nebulized saline or 2 mg of nebulized glucagon. Spirometry was performed at 5, 15, and 30 minutes after treatment. Subjects then received 2.5 mg of nebulized albuterol and had spirometry 15 and 30 minutes thereafter. Each subject returned for testing with the alternative solution at least 1 week later. Treatment with nebulized glucagon resulted in a 58% ± 15% improvement in FEV 1 15 minutes after treatment compared with 36% ± 7% after nebulized saline ( P < .05). No adverse effects of glucagon treatment occurred. This study suggests that nebulized glucagon reduces methacholine-induced bronchospasm in asthmatic patients.

A New Index of Prognostic Severity for Chronic Asthma

To develop a prognostic clinical index for adults with chronic stable asthma. Analysis of data from a 48-week randomized, crossover trial of regular vs as-needed inhaled beta-agonist therapy. Eligible patients included 70 men and women between the ages of 15 and 64 years with asthma for > 1 year. Asthma deterioration within 20 weeks, defined as either a marked decline in FEV1 (> or = 1.0 L or > or = 30% from baseline) or initiation of systemic corticosteroid therapy for asthma exacerbation. Three baseline factors independently predicted asthma deterioration: frequent symptoms on waking in the 4 weeks before baseline, past hospitalization for asthma, and age 35 years or older. Based on cross-stratification and consolidation of these prognostic factors, an index was developed that stratified subjects into four risk groups with distinctive deterioration rates of 9%, 21%, 39%, and 67% (p<0.001). For adults with chronic stable asthma, three simple clinical factors can be combined to stratify effectively for risk of subsequent asthma deterioration.

Treatment of Spontaneous Pneumothorax: A More Aggressive Approach?

emphysema-like changes A New Index of Prognostic Severity for Chronic AsthmaCHESTVol. 112Issue 3PreviewTo develop a prognostic clinical index for adults with chronic stable asthma. Full-Text PDF

Do sputum eosinophils and ECP relate to the severity of asthma?

There is much evidence that eosinophils play an important role in bronchial epithelial damage in asthma by releasing cationic proteins. However, the extent to which eosinophil inflammation relates to indices of asthma severity in chronic stable asthma is still a matter of debate. We studied 46 clinically stable patients with mild to severe chronic asthma (forced expiratory volume in one second (FEV1) 50-126% of predicted value). The clinical severity of asthma was graded from 1 to 4 according to the Aas scoring system. Twelve normal subjects were also studied as controls. Induction of sputum was performed by hypertonic saline to determine differential cell count, and eosinophil cationic protein (ECP) by the so-called "plug technique". The concentration of ECP was measured by a fluoroimmunoassay. Bronchial hyperresponsiveness was recorded by inhaling progressive concentrations of histamine, and the concentration that caused a 20% decrease in FEV1 (PC20) was calculated. Sputum eosinophils (range 0-61%), sputum ECP (range 24-10,800 microg x L[-1]) and serum ECP (range 4-61 microg x L[-1]) were significantly greater in asthmatics than in normal subjects, and distinguished the most severe group with the highest Aas score from the others. Sputum eosinophils and sputum ECP were strongly related to each other. The relationships between sputum or serum ECP and PC20 (range 0.016-7.5 mg x mL[-1]), and between sputum ECP and FEV1 were found to be weak. In conclusion, sputum outcomes of eosinophil activation and serum eosinophilic cationic protein appear to be useful indicators of disease. They do not accurately reflect current clinical or functional indices of asthma severity in chronic stable patients, and might therefore provide complementary data disease monitoring.

Pharmacology of leukotriene receptor antagonists and 5-lipoxygenase inhibitors in the management of asthma.

The leukotrienes (LTs), a family of inflammatory mediators arising from the metabolism of arachidonic acid via the 5-lipoxygenase pathway, are prominently implicated in the pathobiology of asthma. Two classes of LTs, the cysteinyl LTs (LTC4, LTD4, and LTE4) and the dihydroxy-LT (LTB4) have been identified, with each class acting via distinct receptors. Inhibition of LT-mediated inflammation can be achieved by either interruption of 5-lipoxygenase action, thereby preventing formation of the LTs, or inhibition at specific LT receptor sites in the airway. Both the 5-lipoxygenase inhibitors and the cysLT receptor antagonists have thus far demonstrated the capacity to improve pulmonary function and reduce symptoms in clinical models of asthma, such as exercise-, aspirin-, or antigen-induced bronchoconstriction, and to improve pulmonary function in patients with mild-to-moderate, chronic stable asthma. The LTs are therefore critical effector molecules in some patients with asthma and important targets in the pharmacologic management of this disease.

Theophylline revisited.

For over 50 years, theophylline has been used regularly for the management of chronic asthma. However, because of its perceived narrow therapeutic index and the fact that it has been considered a weak bronchodilator, the use of theophylline therapy has diminished. Furthermore, with the introduction of newer pharmacologic agents and recommendations in widely accepted guidelines, both nationally and internationally, have further contributed to its decreased use. For years, theophylline has not only been considered a bronchodilator, but for many clinicians, an agent that could be used to enhance respiratory muscle function and mucociliary clearance and act at the level of the central nervous system to enhance ventilation. These properties were felt to be potentially useful for patients with severe exacerbated asthma. Recent studies have suggested that theophylline therapy can play a beneficial role in the management of both chronic stable asthma and exacerbated disease treated in the emergency department setting. Furthermore, a growing body of evidence suggests that theophylline has certain antiinflammatory and immunomodulating properties, even at plasma concentration levels below the accepted therapeutic range. If this is true, then theophylline may act best as a controller medication in the management of asthma. Because of its low cost and its ease of administration, theophylline therapy should be revisited and discussed as not only a reliever of bronchospasm, but a controller of chronic asthma.

Circulating leukocyte adhesion molecules in stable asthma and nonobstructive chronic bronchitis.

Leukocyte adhesion molecules have been associated with airway inflammatory diseases such as asthma and obstructive chronic bronchitis. Lately, it has become possible to measure circulating forms of cell adhesion molecules (cCAMs) in body fluids. Elevated serum levels have been found in acute asthma and in obstructive chronic bronchitis. We investigated whether the patterns of cICAM-1, cVCAM-1, and cE-selectin could serve as markers for airway inflammation in stable asthma and stable nonobstructive chronic bronchitis. Small-volume bronchial lavage (BL) and serum from 15 controls, 13 asthmatics without steroid inhalation therapy, 11 asthmatics with regular steroid inhalation therapy, and 10 smokers with chronic bronchitis were analyzed. We found cICAM-1, cVCAM-1, and cE-selectin to be present in serum from patients with stable asthma and stable nonobstructive chronic bronchitis. Only cICAM-1 was found in BL fluid. No differences were seen between the subject groups for either cCAM, but levels of ECP were increased in the non-steroid-treated asthmatic group. Subject atopy or smoking did not increase the cCAM levels. In conclusion, the degree of airway inflammation in stable nonobstructive chronic bronchitis and stable asthma does not appear to be well associated with circulating ICAM-1, cVCAM-1, and cE-selectin.

Lack of Effectiveness of Magnesium in Chronic Stable Asthma

Lack of Effectiveness of Magnesium in Chronic Stable Asthma

ARE THEOPHYLLINES BEING PRESCRIBED EFFECTIVELY AND SAFELY IN GENERAL PRACTICE?

SUMMARY To investigate the attitudes and practices of GPs towards the use and monitoring of theophyllines, a questionnaire was mailed to all 479 GP principals in Nottinghamshire with one reminder to non‐responders. Valid responses were obtained from 49% (236). Theophyllines were regarded as first‐line or frequent second‐line bronchodilators by 40% (94 of 234) of GPs in chronic bronchitis, 24% (56 of 234) in nocturnal asthma, and by 6% (15 of 234) in chronic stable asthma, although only 1% (2 of 234) of GPs regarded theophylline as strictly first‐line therapy in chronic stable asthma. Theophylline levels were never checked by 76% (172 of 225) of practitioners at the start of therapy, or by 48% (110 of 231) during long‐term therapy; half (110 of 217) could identify only up to 50% of a series of common factors affecting theophylline levels. There was no relationship between a score of theophylline knowledge and prescribing habits in chronic bronchitis, but doctors who checked levels scored significantly higher. Although theophyllines are being used in general practice for broadly sensible indications, this survey highlights aspects of prescribing that may be compromising both safety and effectiveness. Patients are likely to benefit if the need to check levels and the factors affecting levels become better known.

Comparison of the Effect of Inhaled Selective and Non-selective Adrenergic Agonists on Cardiorespiratory Parameters in Chronic Stable Asthma

Summary: Increased hypoxia has been found after β2 adrenoceptor agonists (but not adrenaline) in asthmatics. Combined with hypokalaemia and sympathomimetic stimulation, this may predispose to cardiac arrhythmias. We have compared the effects of nebulized adrenaline and a selective β2 agonist (salbutamol) on the arterial oxygen saturation (SaO2), minute ventilation (V̇E), forced expiratory volume in 1 s (FEV1), plasma potassium and the electrocardiogram (ECG) in patients with chronic stable asthma. Six patients were studied according to a randomized, placebo-controlled, double-blind cross-over protocol. Adrenaline (5 mg), salbutamol (5 mg) and placebo were administered during 4 min tidal breathing using a nebulizer driven by air. There was a fall in SaO2 after both adrenaline (mean % fall (SEM) 3.3 (0.2)) and salbutamol (4.0 (0.7)) associated with an increase in FEV1, with no change in V̇ E. Therefore, the fall in SaO2 must have been caused by increased ventilation-perfusion imbalance. There was an increased heart rate after both adrenaline and salbutamol and ventricular ectopic beats and a short run of parasystole were recorded on the ECG in one patient after adrenaline and in two patients after sulbutamol. No change was found in plasma potassium levels. We conclude that both adrenaline and a selective β2 agonist salbutamol can cause a fall in SaO2 and ventricular ectopy in some asthmatic patients.

Eosinophil activity in bronchial asthma.

Eosinophil cationic proteins (ECP), eosinophil protein X (EPX), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), and the major basic protein (MBP) have been identified as potent cytotoxic secretory proteins in degranulated eosinophils. Studies of these proteins have clearly indicated a role for eosinophil-derived proteins in inflammatory diseases, including asthmatic inflammation. It has been shown that higher levels of ECP in asthmatics were concomitant with severity of the disease and related to efficacy of treatment of asthma. Proper handling of blood serum for measurement of eosinophil and neutrophil markers including myeloperoxidase (MPO) is essential. Moreover, the time factor in ECP measurement is an important variable because ECP levels differ in chronic stable asthma, during acute exacerbations of asthma, and after allergen challenge. Simultaneous measurements of ECP and MPO may prove to be useful in determining various causes of asthma exacerbations, helping to discriminate between allergic etiologies wherein ECP levels may increase versus infectious etiologies wherein MPO levels may increase. Monitoring the efficacy of anti-inflammatory therapies such as corticosteroids may be enhanced by serial determinations of ECP levels in the blood.

The Role of Antigen Detection in Pneumococcal Carriers: A Comparison between Cultures and Capsular Antigen Detection in Upper Respiratory Tract Secretions

During the winter season upper respiratory tract secretions from 166 patients with stable chronic obstructive pulmonary disease (COPD) or asthma were simultaneously cultured for Streptococcus pneumoniae and tested for pneumococcal capsular antigen. Latex agglutination was employed to investigate the effect of pneumococcal carriership on pneumococcal capsular antigen detection in upper respiratory tract secretions. All specimens originating from the oropharynx, nasopharynx and saliva were both cultured and investigated in parallel for the presence of antigen. The recovery of pneumococci from the different areas was unequally distributed (oropharynx 29%, nasopharynx 8%, and saliva 16%), with the highest isolation rate from the oropharynx alone. Only 4 (3%) of the oropharyngeal swabs, 1 (1%) of the nasopharyngeal swabs and 14 (9%) of the saliva specimens yielded both pneumococcal antigen and a positive culture for S. pneumoniae. A further 9 (6%) of the oropharyngeal swabs, 5 (3%) of the nasopharyngeal swabs, and 50 (33%) of the saliva specimens were antigen positive only, with no pneumococci isolated on culture. It is speculated that these reactions were due to cross-reacting microorganisms (especially alpha-haemolytic streptococci) present in saliva and contaminating the oropharynx and the nasopharynx. Quantitative cultures of 9 oropharyngeal swabs yielded S. pneumoniae in concentrations too low to be detectable by latex agglutination. The study indicates that there is a poor relation between pneumococcal colonization and antigen detection in the oropharynx and nasopharynx. Antigen present in these secretions is probably not an important disrupting factor by contamination when detecting pneumococcal antigen in washed sputum. The false positive antigen results in saliva are probably due to cross-reactions with alpha-haemolytic streptococci.

The Role of Antigen Detection in Pneumococcal Carriers: A Comparison between Cultures and Capsular Antigen Detection in Upper Respiratory Tract Secretions

During the winter season upper respiratory tract secretions from 166 patients with stable chronic obstructive pulmonary disease (COPD) or asthma were simultaneously cultured for Streptococcus pneumoniae and tested for pneumococcal capsular antigen. Latex agglutination was employed to investigate the effect of pneumococcal carriership on pneumococcal capsular antigen detection in upper respiratory tract secretions. All specimens originating from the oropharynx, nasopharynx and saliva were both cultured and investigated in parallel for the presence of antigen. The recovery of pneumococci from the different areas was unequally distributed (oropharynx 29%, nasopharynx 8%, and saliva 16%), with the highest isolation rate from the oropharynx alone. Only 4 (3%) of the oropharyngeal swabs, 1 (1%) of the nasopharyngeal swabs and 14 (9%) of the saliva specimens yielded both pneumococcal antigen and a positive culture for S. pneumoniae. A further 9 (6%) of the oropharyngeal swabs, 5 (3%) of the nasopharyngeal swabs, and 50 (33%) of the saliva specimens were antigen positive only, with no pneumococci isolated on culture. It is speculated that these reactions were due to cross-reacting microorganisms (especially alpha-haemolytic streptococci) present in saliva and contaminating the oropharynx and the nasopharynx. Quantitative cultures of 9 oropharyngeal swabs yielded S. pneumoniae in concentrations too low to be detectable by latex agglutination. The study indicates that there is a poor relation between pneumococcal colonization and antigen detection in the oropharynx and nasopharynx. Antigen present in these secretions is probably not an important disrupting factor by contamination when detecting pneumococcal antigen in washed sputum. The false positive antigen results in saliva are probably due to cross-reactions with alpha-haemolytic streptococci.

The effect of GR32191 (a thromboxane receptor antagonist) on airway responsiveness in asthma

Airway responsiveness to methacholine was measured in nine subjects (22–53 years, seven male) with chronic stable asthma. All subjects were taking inhaled beclomethasone (<1000 μg daily). The mean baseline FEV 1, was 2.841 (77% of predicted) and the geometric mean PD 20FEV 1, was 31 μg. After a run-in period, the subjects were randomly allocated to two treatment periods with the specific thromboxane receptor antagonist GR32191, 40 mg four times daily for 3 weeks, and identical placebo capsules. A double-blind, placebo-controlled, cross-over design was employed with 4 weeks between the two treatment periods. Treatment with GR32191 did not result in any significant improvement in mean FEV 1, (2.941 after placebo and 2.861 after GR32191; F 7,71 = 1.02, P>0.1) or PD 20FEV 1, (24.3 μg after placebo and 38.5 μg after GR32191; F 7,71 = 0.59, P>0.1). We conclude that thromboxane is not important in the maintenance of airway hyperresponsiveness in chronic asthma and that thromboxane receptor antagonists are unlikely to provide effective treatment for this group of patients.