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Asthma is best described as a chronic disease that involves inflammation of the pulmonary airways and bronchial hyperresponsiveness that results in the clinical expression of a lower airway obstruction that usually is reversible. Physiologically, bronchial hyperresponsiveness is documented by decreased bronchial airflow after bronchoprovocation with methacholine or histamine. Other triggers that provoke airway obstruction include cold air, exercise, viral upper respiratory infection, cigarette smoke, and respiratory allergens. Bronchial provocation with allergen induces a prompt early phase immunoglobulin E (IgE)-mediated decrease in bronchial airflow (forced expiratory volume in 1 second) followed in many patients by a late-phase IgE-mediated reaction with a decrease in bronchial airflow for 4-8 hours. The gross pathology of asthmatic airways displays lung hyperinflation, smooth muscle hypertrophy, lamina reticularis thickening, mucosal edema, epithelial cell sloughing, cilia cell disruption, and mucus gland hypersecretion. Microscopically, asthma is characterized by the presence of increased numbers of eosinophils, neutrophils, lymphocytes, and plasma cells in the bronchial tissues, bronchial secretions, and mucus. Initially, there is recruitment of leukocytes from the bloodstream to the airway by activated CD4 T-lymphocytes. The activated T-lymphocytes also direct the release of inflammatory mediators from eosinophils, mast cells, and lymphocytes. In addition, the subclass 2 helper T-lymphocytes subset of activated T-lymphocytes produces interleukin (IL)-4, IL-5, and IL-13. IL-4 in conjunction with IL-13 signals the switch from IgM to IgE antibodies. The cross-linkage of two IgE molecules by allergen causes mast cells to degranulate, releasing histamine, leukotrienes, and other mediators that perpetuate the airway inflammation. IL-5 activates the recruitment and activation of eosinophils. The activated mast cells and eosinophils also generate their cytokines that help to perpetuate the inflammation. Regardless of the triggers of asthma, the repeated cycles of inflammation in the lungs with injury to the pulmonary tissues followed by repair may produce long-term structural changes ("remodeling") of the airways. This review will discuss in greater detail the relationships of inflammation and airway hyperresponsiveness to the pathophysiology of asthma.

Purpose: Adherence to peak expiratory flow rate monitoring by children with asthma was evaluated, and a behavioral strategy to enhance adherence to daily monitoring was tested., Design and Methods: Forty-two 7- through 11-year-old children with persistent asthma were recruited into a 5-week randomized, controlled clinical trial. Adherence data were collected electronically by PeakLog and the self-report Asthma Diary., Results: Adherence declined over time. At week 5, intervention group adherence (Median = 79%) was higher than the usual care group adherence (Median = 64%), but the difference was not statistically significant. The effect size did suggest that differences between groups were present., Conclusions: Even small improvements in adherence to asthma treatment may be clinically significant in light of the alarming increases in asthma morbidity and mortality. Contingency management shows promise for improving adherence outcomes. Future research should engage larger sample sizes and increase the number and intensity of sessions to teach behavioral strategies.

Study Objective: Clinical trials of asthma treatments usually use measures of asthma control to assess efficacy. However, it is also important to determine whether patients themselves benefit from interventions. The aim of this study was to evaluate health-related quality of life in patients with asthma switched from conventional chlorofluorocarbon (CFC) beclomethasone dipropionate (BDP) to hydrofluroalkane-134a (HFA) BDP extrafine aerosol at half the daily dose., Design: Open-label, 12-month, parallel-group, randomized trial., Setting: Fifty-seven centers in four countries (United States, Belgium, the Netherlands, and United Kingdom)., Patients: Four hundred seventy-three patients with a > or = 6-month history of asthma, stable symptoms, and maintained on CFC-BDP, 400 to 1,600 microg/d., Interventions: HFA-BDP, 200 to 800 microg/d (n = 354), or CFC-BDP, 400 to 1,600 microg/d (n = 119)., Measurements and Results: The Asthma Quality of Life Questionnaire (AQLQ) and pulmonary function tests were completed at months 0, 2, 4, 8, and 12. For 1 month before each visit, patients made daily recordings of symptoms, peak expiratory flow, and beta(2)-agonist use. Two hundred ninety-six patients completed the study (HFA-BDP, 83.6%; CFC-BDP, 83.2%). At month 12, improvements in overall AQLQ scores were greater in the HFA-BDP group than in the CFC-BDP group (p = 0.0024). The number of patients who need to be treated with HFA-BDP for one to have a clinically important improvement in overall asthma-specific quality of life compared with CFC-BDP was 7.3. There was no evidence of differences (p > 0.05) between treatment groups for airway caliber, symptoms, or beta(2)-agonist use., Conclusion: Clinically important improvements in the AQLQ score were observed at month 12 for HFA-BDP vs CFC-BDP, while conventional clinical indexes of pulmonary function and asthma control were similar in the two groups.

Severe persistent asthma accounts for a small percentage, probably less than 5% of all patients with asthma, but is responsible for the major portion of health care costs associated with the illness. According to the National Institutes of Health (National Asthma Education and Prevention Program) guidelines for the management of asthma, patients with severe asthma should be treated with high dosages of inhaled corticosteroids. These inhaled corticosteroids can be given in conjunction with a brief course of oral or parenteral systemic steroids, but it is best to decrease or eliminate systemic corticosteroid therapy whenever possible to prevent the side effects of long-term oral prednisone therapy. If inhaled corticosteroids do not control the asthma, then one or perhaps two, and even three, other long-term control medications can be added to the therapy regimen. Current guidelines recommend adding a long-acting beta 2-agonist such as salmeterol to the inhaled corticosteroid. Recent evidence suggests that leukotriene receptor antagonists can also be used in conjunction with inhaled steroids. Theophylline is also recommended as another controller agent to be considered. Unfortunately, no studies have comparatively evaluated all of these different classes of agents, even in moderate asthma, in head-to-head trials. This manuscript will review the current literature and provide the author's perspective on the combination of these medications in the pharmacologic management of moderate to severe persistent asthma.

Asthma is a chronic inflammatory disease of the lower airways. Epidemiologic surveys and clinical reports have documented that allergic rhinitis coexists with asthma in many patients. Provocative bronchial challenge with allergens responsible for allergic rhinitis in susceptible asthma patients can elicit asthma, and these responses have been linked to bronchial airway hyperreactivity. Provocative bronchial methacholine challenge in allergic rhinitis patients will demonstrate increased airway responsiveness to the bronchial challenge in 30% of those allergic rhinitis patients who had no past history of asthma. These data suggest that subclinical asthma may be present in certain patients with allergic rhinitis. The focus of the National Heart, Lung, and Blood Institute (NHLBI) guidelines for the pharmacologic treatment of asthma focuses on medications to relieve the symptoms of asthma, i.e., bronchodilators and anti-inflammatory agents (i.e., inhaled corticosteroids, cromolyn, and leukotriene modifiers) to control asthma. Avoidance of allergens such as house dust mite are also recommended. Although not emphasized in these NHLBI guidelines, recent studies have observed that treatments, including intranasal steroid, cromolyn, antihistamines, and decongestants, which provide relief of nasal symptoms in patients with both allergic rhinitis and asthma, will also improve the pulmonary symptoms of allergic asthma. This article will review the recent literature.

Increasing prevalence and severity of asthma has prompted the development and promulgation of various national and international guidelines for asthma management in adults and children. All of these guidelines agree that short-acting inhaled B2-agonists on demand represent the most appropriate initial bronchodilator therapy. However, there has been considerable debate as to the merit of maintenance bronchodilator therapy with regular inhaled B2-agonists, either the short acting agents, or the newer long-acting inhaled B2-agonist, salmeterol. Of concern is the possibility that there are detrimental effects of chronic B2-agonist bronchodilator treatment. Do these B2-agonists have the potential to worsen asthma control and thereby have an adverse impact by contributing to the increased prevalence and severity of asthma? This article will review the pertinent literature with regard to the safety of the B2-agonists, which are appropriate but not perfect medications for asthmatics. It will also put this information in perspective for the clinician and provide this author's recommendations for their use in managing the manifestations of chronic and recurrent asthma.

Asthma is a multifactorial, reversible, obstructive lung disease that manifests airway inflammation as well as airway hyperreactivity. In addition to IgE-mediated respiratory reactions, the pathophysiology of asthma can be triggered by both viral respiratory and bacterial sinopulmonary infections. Even though most asthma patients do not manifest undue susceptibility to infection, a subset of asthma patients with recurrent sinopulmonary as well as upper-respiratory infections may have an associated immune deficiency syndrome. In a subset of these patients, deficiencies of serum IgG subclasses have also been described in the presence of low-normal or normal serum IgG and also deficient serum IgA. In addition to the usual asthma therapy with beta 2 agonist and theophylline bronchodilators as well as cromolyn and steroids, many of these immunodeficiency patients will benefit from iv gamma-globulin therapy. However, we suggest that an inability to synthesize specific serum antibody to injected vaccines or immunogens be a prerequisite before initiating iv gamma-globulin therapy. The clinician should not rely on serum IgG subclass levels alone as a criterion for initiation of passive immune globulin therapy. There may be another cohort of asthma patients who could benefit from iv gamma-globulin therapy. In a small open-label pilot study severe steroid-dependent asthma patients who were not immunodeficient and did not have undue susceptibility to infection were treated with iv gamma-globulin with a very large dosage protocol of 2000 mg/kg monthly.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent studies of laboratory-provoked asthma have suggested that asthma is an inflammatory disease of lower airways. The purpose of this study was to measure the systemic elaboration of 2 bronchoconstrictive inflammatory mediators during naturally acquired acute asthma utilizing a prospective, serial-sampling protocol. Plasma levels of 13,14-dihydro-15-keto-PGF2 alpha and histamine were measured by radioimmunoassay and radioenzymatic assay, respectively, in 23 children with acute asthma. Mean PG metabolite and histamine values (pg/ml) before (167 +/- 72, 1,029 +/- 378) and 10 to 90 min after (377 +/- 145, 1,000 +/- 489) initial therapy were significantly higher than those of the same children after resolution of asthma (2.9 +/- 0.2, 260 +/- 42) and those of normal children (4.3 +/- 0.9, 240 +/- 14). Peak PG metabolite levels were significantly higher in children who presented with PEFR values (% predicted) less than 40% (1,234 +/- 432) compared with those who presented with greater than 40% (404 +/- 296), and in children with post-therapy improvement in PEFR of less than 20% (1,281 +/- 470) compared with those with greater than 20% (365 +/- 226). Histamine levels were significantly higher in children with post-therapy improvement in PEFR of less than 20% (2,560 +/- 1,600) compared with those with greater than 20% (475 +/- 100), and in hospitalized (3,915 +/- 1,910) compared with nonhospitalized (408 +/- 130) children. Significant differences were not observed on the basis of corticosteroid dependence, allergic disposition, or type of initial therapy. These data suggest a role for histamine and PGF2 alpha in the pathogenesis of airway inflammation in acute asthma.

A hydrocortisone preparation containing methylparaben and propylparaben provoked bronchospasm and pruritus when given intravenously to an asthmatic patient, whereas another hydrocortisone preparation without paraben preservative did not. Direct and passive transfer (Prausnitz-Küstner) skin tests for immediate hypersensitivity to parabens were positive. Parabens, frequently employed as bacteriostatic agents, are capable of producing immunologically mediated, immmediate systemic hypersensitivity reactions.

Morbidity and mortality of asthma has been on the upswing since the 1960s, as marked by increased hospitalizations with asthma since the early 1980s. This has not been explained adequately. The possibility of change in the natural history or increased exposure to environmental irritant chemicals or allergens has been suggested by some. There probably has been better recognition and diagnosis of asthma by distinguishing it from bronchitis, recurrent croup, and bronchiolitis in children. Despite evidence to suggest that this is the case, there are still some missing factors. The increase in asthma mortality is more understandable when one considers the fact the management of asthma has changed greatly in the past two decades. The use of corticosteroids orally, parenterally, and by inhalation has been a double-edged sword. There is no doubt that many asthmatics have a much improved sense of well-being and have lived more normal lives due to the use of corticosteroids. The inability of some patients, parents, or physicians to perceive impending respiratory difficulty, however, may result in underuse of drugs, including corticosteroids, leading to increased mortality. Other factors have led to increased mortality from asthma in recent years, and they include arrhythmias with combinations of theophylline, beta-agonists, and hypoxia. The psychological factors attendant to adolescence and psychological problems are probably quite important in the recent upsurge in asthma deaths in the 15- to 25-year age group. Many deaths are occurring outside of the hospital environment and may be largely preventable. There must be increased awareness by the patient, the family, and the physician. In view of the increased hospitalizations, the total number of deaths is not increasing at an alarming rate, yet it is necessary to make all of us who care for asthmatics aware and take corrective action as soon as we are aware of an asthmatic with respiratory problems.

A program designed to teach self-management skills to asthmatic children and their parents was performed by a nurse-educator utilizing health education techniques. Goals included: (1) reduce frequency and severity of asthma; (2) reduce emergency room visits and hospitalizations; (3) reduce school absenteeism; (4) develop positive family self-help attitudes; and (5) incorporate patient-parent education in an office. After informed consent was obtained, 26 asthmatic children, aged 2 to 14 years, were selected and evaluated. Appropriate asthma management including avoidance, medications, and immunotherapy, if indicated, was initiated for both a study group (13 patients) and a comparison group (13 patients). Symptom and medication diaries were kept for six to 18 months. Educational intervention by a nurse-educator, including four hours of individual instruction, group classes, telephone access, and monitoring for the study patients, resulted in fewer hospitalizations and emergency room visits as compared to control patients, tenfold less school absenteeism, and fewer asthma attacks. Estimated hospital and emergency room costs were much less in the educated group. These results were accomplished by improving comprehension of and compliance with the medical management program by the study patients and their families; more medications were used and therapy for asthma was initiated earlier.

Perception of respiratory function may be an important factor in self-management of asthma. Previous research has suggested that asthmatics may not accurately perceive pulmonary functioning. The perception of normal and asthmatic individuals was assessed using a magnitude production procedure in a series of three studies, proceeding from normal individuals during rest, then submaximal exercise, to a comparison of normal and asthmatic adolescents during rest and submaximal exercise. At rest there were no differences between males and females, adults and adolescents, or asthmatics and non-asthmatics. However, there were significant differences in perception between rest and exercise for all groups. These findings suggest that a breakdown in perception does not occur during submaximal exercise in patients with asthma.

Radial immunodiffusion was used to measure the concentrations of IgG, IgA, and IgM in the sera of 224 asthmatic children, ages 6 months to 14 years. IgM was greater than two standard deviations above age-matched normal values in 51% of these asthmatic subjects. Immunoglobulin profiles were repeated up to four years later in 29 individuals with elevated IgM and increased IgM synthesis was sustained in 14 of these asthmatic subjects. Serum IgE concentrations were elevated in 23 of 35 asthmatic patients. There was no statistical difference in mean IgE between asthmatic children with normal or increased IgM. The distribution of IgE in each group was similar. Only 10 of 224 subjects had an IgA concentration less than 2 SD below age-matched control subjects. The significance and possible mechanisms of hyper-M-immunoglobulinemia are discussed.

Sinusitis has been considered to be a possible causal factor for asthma. Reflex has also been postulated between the upper and lower airway. Data for and against the existence of such a reflex are presented, together with the diagnosis and management of sinusitis.

Signs, symptoms, and radiographic abnormalities of sinusitis are frequent in children with asthma; it is not known whether sinus inflammation is associated with bacterial infection or other mechanisms. Eight asthmatic patients with exacerbation of asthma despite bronchodilator therapy were studied after maxillary sinusitis was confirmed by radiographs. All had cough, wheezing, nasal stuffiness, rhinorrhea and were afebrile. Four patients had headaches, and two had facial pain. Maxillary sinus aspirates were obtained, and bacterial cultures were positive in five: Branhamella catarrhalis (2), nontypeable Hemophilus influenzae (2), Streptococcus pneumoniae (1). Nose and throat cultures did not correlate with sinus cultures. All patients received bronchodilators, and four of eight patients received steroids. All were treated for 14 to 28 days with antibiotics during which seven of the eight patients improved clinically including all with positive sinus cultures. Asthma-symptoms diary scores were kept by five; all demonstrated improvement. Pulmonary-function tests improved in five of seven patients after the antibiotic and asthma therapy including the four patients with positive cultures. Sinus radiographs cleared in three, improved in three, and were unchanged in two patients after antibiotic therapy.

Asthma is best described as a chronic disease that involves inflammation of the pulmonary airways and bronchial hyperresponsiveness that results in the clinical expression of a lower airway obstruction that usually is reversible. Physiologically, bronchial hyperresponsiveness is documented by decreased bronchial airflow after bronchoprovocation with methacholine or histamine. Other triggers that provoke airway obstruction include cold air, exercise, viral upper respiratory infection, cigarette smoke, and respiratory allergens. Bronchial provocation with allergen induces a prompt early phase immunoglobulin E (IgE,)- mediated decrease in bronchial airflow (forced expiratory volume in 1 second) ,followed in many patients by a late-phase IgE- mediated reaction with a decrease in bronchial airflow ,for 4-8 hours. The gross pathology of asthmatic airways displays lung hyperinflation, smooth muscle hypertrophy, lamina reticularis thickening, mucosal edema, epithelial cell sloughing, cilia cell disruption, and mucus gland hypersecretion. Microscopically, asthma is characterized by the presence of increased numbers of eosinophils, neutrophils, lymphocytes, and plasma cells in the bronchial tissues, bronchial secretions, and mucus. Initially, there is recruitment of leukocytes from the bloodstream to the airway by activated CD[&4sub;] T-lymphocytes. The activated T-lymphocytes also direct the release of inflammatory mediators from eosinophils, mast cells, and lymphocytes. In addition, the subclass 2 helper T-lymphocytes subset of activated T-lymphocytes produces interleukin (IL)-4, IL-5, and IL-13. IL-4 in conjunction with IL-13 signals the switch from 1gM to IgE antibodies. [ABSTRACT FROM AUTHOR]