Differences between asthma exacerbations and poor asthma control

BACKGROUND: Increased variation in peak expiratory flow (PEF) is characteristic of poorly controlled asthma, and measurement of diurnal variability of PEF has been recommended for assessment of asthma severity, including during exacerbations. We aimed to test whether asthma exacerbations had the same PEF characteristics as poor asthma control. METHODS: Electronic PEF records from 43 patients with initially poorly controlled asthma were examined for all exacerbations that occurred after PEF reached a plateau with inhaled corticosteroid treatment. Diurnal variability of PEF was compared during exacerbations, run-in (poor asthma control), and the period of stable asthma before each exacerbation. FINDINGS: Diurnal variability was 21.3% during poor asthma control and improved to 5.3% (stable asthma) with inhaled corticosteroid treatment. 40 exacerbations occurred in 26 patients over 2-16 months; 38 (95%) of exacerbations were associated with symptoms of clinical respiratory infection. During exacerbations, consecutive PEF values fell linearly over several days then improved linearly. However, diurnal variability during exacerbations (7.7%) was not significantly higher than during stable asthma (5.4%, p=0.1). PEF data were consistent with impaired response to inhaled beta2-agonist during exacerbations but not during poorly controlled asthma. INTERPRETATION: Asthmatics remain vulnerable to exacerbations during clinical respiratory infections, even after asthma is brought under control. Calculation of diurnal variability may fail to detect important changes in lung function. PEF variation is strikingly different during exacerbations compared with poor asthma control, suggesting differences in beta2-adrenoceptor function between these conditions.     

Effect of long-term treatment with salmeterol on asthma control: a double blind, randomised crossover study

OBJECTIVES: To determine the effect of adding salmeterol 50 micrograms twice daily for six months to current treatment in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. DESIGN: A double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101 subjects with mild or moderate asthma taking at least 200 micrograms twice daily of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50 micrograms twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. RESULTS: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroids. For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use and airway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-response study. CONCLUSIONS: In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control.     

Chemical and pharmacological studies of Phyllanthus caroliniensis in mice

We studied retrospectively the effect of long-term treatment with an inhaled corticosteroid on bronchial hyperresponsiveness (BHR) and clinical asthma in moderate-severe asthmatic subjects. Fifty-eight patients who had used beclomethasone dipropionate (BDP) over one year, were enrolled in this study. BHR was measured before and after treatment with BDP by the methods recommended by Japanese Society of Allergology. Moreover we examined the clinical factors and the frequency of acute exacerbations. The results as follows: 1) The mean age was 48.8 years and the mean asthma history was 9.2 years. The mean dose and mean time of BDP administration was 801 micrograms/day and 28.1 months, respectively. 2) Patients during BDP treatment over one year showed about 6-fold mean improvements in BHR, but there were many patients who showed no improvements in BHR. 3) We retrospectively divided all the patients into two groups. Namely, the improved group (n = 25) showed more than 4 fold improvement in BHR and unchanged group (n = 33), less than 4-fold. But there were no significant differences in clinical characteristics and %FEV1 during treatment with BDP. 4) The unchanged group had more near fatal episodes in the past than the improved group. 5) There was significant decrease in acute exacerbation during treatment with BDP, but the unchanged group had more acute exacerbations than the improved group during treatment with BDP. These results indicates that there are many patients who had no improvement on BHR with long term BDP treatment and they have more acute exacerbations due to various stimuli. In conclusion, asthma is recognized chronic inflammatory disease and inhaled corticosteroid therapy has been recommended as the first line therapy. We must further study the clinical problems and underlying mechanisms concerning about treatment with an inhaled corticosteroid.     

Inhaled nitric oxide for adult respiratory distress syndrome after pulmonary resection

BACKGROUND: The adult respiratory distress syndrome (ARDS) developing after pulmonary resection is usually a lethal complication. The etiology of this serious complication remains unknown despite many theories. Intubation, aspiration bronchoscopy, antibiotics, and diuresis have been the mainstays of treatment. Mortality rates from ARDS after pneumonectomy have been reported as high as 90% to 100%. METHODS: In 1991, nitric oxide became clinically available. We instituted an aggressive program to treat patients with ARDS after pulmonary resection. Patients were intubated and treated with standard supportive measures plus inhaled nitric oxide at 10 to 20 parts/million. While being ventilated, all patients had postural changes to improve ventilation/perfusion matching and management of secretions. Systemic steroids were given to half of the patients. RESULTS: Ten consecutive patients after pulmonary resection with severe ARDS (ARDS score = 3.1+/-0.04) were treated. The mean ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen at initiation of treatment was 95+/-13 mm Hg (mean +/- SEM) and improved immediately to 128+/-24 mm Hg, a 31%+/-8% improvement (p<0.05). The ratio improved steadily over the ensuing 96 hours. Chest x-rays improved in all patients and normalized in 8. No adverse reactions to nitric oxide were observed. CONCLUSIONS: We recommend the following treatment regimen for this lethal complication: intubation at the first radiographic sign of ARDS; immediate institution of inhaled nitric oxide (10 to 20 parts per million); aspiration bronchoscopy and postural changes to improve management of secretions and ventilation/perfusion matching; diuresis and antibiotics; and consideration of the addition of intravenous steroid therapy.     

Slowing the deterioration of asthma and chronic obstructive pulmonary disease observed during bronchodilator therapy by adding inhaled corticosteroids. A 4-year prospective study

OBJECTIVE: To determine if deterioration in patients with asthma or chronic obstructive pulmonary disease (COPD) during bronchodilator therapy could be slowed by additional treatment with an inhaled corticosteroid. DESIGN: A 4-year prospective study. SETTING: Twenty-nine general practices in the catchment area of the University of Nijmegen, Nijmegen, the Netherlands. PATIENTS: The study included 56 patients (28 with asthma and 28 with COPD) who showed an annual decrease in the forced expiratory volume in 1 second (FEV1) of at least 80 mL in combination with at least two exacerbations per year during bronchodilator therapy alone. Forty-eight patients completed the study. INTERVENTION: During the first 2 years of treatment, patients received only bronchodilator therapy (salbutamol, 400 micrograms, or ipratropium bromide, 40 micrograms). During years 3 and 4, they received additional treatment with beclomethasone dipropionate, 400 micrograms two times daily. RESULTS: Prebronchodilator FEV1 increased 458 mL/y (95% CI, 233 to 683 mL/y) during the first 6 months of beclomethasone treatment; FEV1 then decreased 102 mL/y (CI, 57 to 147 mL/y) during months 7 to 24. The annual decline in FEV1 during beclomethasone treatment was less than the decline of 160 mL/y seen before beclomethasone therapy (difference, 58 mL/y; 95% CI, 2 to 87 mL/y). Only in patients with asthma did beclomethasone treatment improve bronchial hyperresponsiveness (assessed by determining the concentration of histamine that provoked a 20% decrease in FEV1 [PC20]) by 3.0 doubling doses per year (95% CI, 0.8 to 5.2 doses per year). Beclomethasone treatment was associated with improvement in peak expiratory flow rate, alleviation of symptoms, and a decrease in the number of exacerbations in both patient groups. CONCLUSIONS: Adding beclomethasone, 800 micrograms daily, slowed the unfavorable course of asthma or COPD seen with bronchodilator therapy alone. This effect was most evident in asthmatic patients.     

Utilization of healthcare resources for asthma in Singapore: demographic features and trends

This study examined the healthcare utilization patterns for asthma in Singapore, a tropical island city-state, between 1986 and 1993. Asthma was ranked fifth among principal conditions with the highest number of discharges in Singapore (2.4 discharges per 1,000 population per annum). Among the 0-14 year-olds, asthma was ranked second, only after accidents and injuries, as the condition with the highest number of discharges (5.2 per 1,000). It was estimated that there were approximately 20,000 accident and emergency (A & E) room visits for asthma per annum (7.0 visits per 1,000 population per annum). There were, however, no significant changes in the number of hospitalized or emergency room cases for asthma over the period of analysis. In the primary healthcare setting, asthma ranked 6th among the leading conditions seen by the general practitioners and government polyclinics (15 visits per 100 population per annum). Among under 15 year olds, asthma (37 visits per 100 age-adjusted population per annum) ranked as the second leading condition behind upper respiratory tract infections. This study has shown that asthma causes a significant amount of morbidity in the Singapore community.     

Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group

BACKGROUND: The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. METHODS: After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days. RESULTS: The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater. CONCLUSIONS: In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.     

The Fresno Asthma Project: a model intervention to control asthma in multiethnic, low-income, inner-city communities

The Fresno Asthma Project targeted the entire low-income, inner-city, multiethnic population of Fresno, California. For 36 months following a 6-month planning phase, continuing education was provided to a high proportion of physicians, pharmacists, nurses/respiratory therapists, emergency medical technicians, school personnel, and allied health professionals involved in asthma care in Fresno, including virtually all those providing care/services to the target population. Small group patient education was made available and provided in age- and culturally appropriate formats to patients/families in clinics, hospitals, and schools. General and ethnic media and a Speakers Bureau were used to raise public awareness of asthma as a serious but controllable health problem. This community intervention model is particularly appropriate to multiethnic communities. It is relatively low cost (total direct costs were $140,000 per year), uses existing educational resources, and appears to have minimized counterproductive competition. Although morbidity and mortality trend data are not yet available to monitor program impact, penetration into the target community has been substantial: community physicians refer patients to asthma classes, asthma educator training is ongoing through the local American Lung Association chapter, hospitals and managed care systems serving low- income/MediCal patients offer asthma classes, and public schools and HeadStart are institutionalizing asthma awareness and self-management classes.     

Noninvasive ventilation in acute respiratory failure

Noninvasive PPV has been employed for decades in patients with chronic respiratory failure. Increasing use in patients with acute respiratory failure is a more recent phenomenon, mainly because of advances in noninvasive interfaces and ventilator modes. Noninvasive PPV delivered by nasal or oronasal mask has been demonstrated to reduce the need for endotracheal intubation, decrease lengths of stay in the ICU and hospital, and possibly reduce mortality. In the acute care setting, evidence now demonstrates the efficacy of noninvasive PPV for acute exacerbations of COPD, pulmonary edema, pulmonary contusions, and acute respiratory failure in patients who decline or who are not believed to be candidates for intubation. No firm conclusions can yet be made regarding patients with respiratory failure due to other causes, but studies suggest that noninvasive PPV may also be of benefit in patients with postoperative respiratory insufficiency, chest wall disease, and cystic fibrosis. Several factors are vital to the success of this therapy, including careful patient selection, properly timed intervention, a comfortable, well-fitting interface, patient coaching and encouragement, and careful monitoring. Noninvasive ventilation should be used as a way to avoid endotracheal intubation rather than as an alternative. Accordingly, a trial of noninvasive ventilation should be instituted in the course of acute respiratory failure before respiratory arrest is imminent, to provide ventilatory assistance while the factors responsible for the respiratory failure are aggressively treated. Moreover, the authors favor conservative management with expeditious intubation in patients who have other conditions that place them at risk during use of noninvasive ventilation or in patients failing to respond to noninvasive PPV. Noninvasive PPV clearly represents an important addition to the techniques available to manage patients with acute respiratory failure; however, because most studies have been retrospective and uncontrolled, many issues remain unresolved. Further controlled studies are needed to confirm the safety and efficacy of noninvasive PPV, evaluate the most appropriate selection of patients and timing of intervention, define the best type of interface, and assess the costs of noninvasive PPV in comparison with conventional therapy.     

High-pressure destruction kinetics of Listeria monocytogenes on pork

OBJECTIVE: To define the incidence of complications of endotracheal intubation and the factors associated with these complications. STUDY DESIGN: During a 22-month period, 227 intubated infants weighing <1,501 g were followed prospectively in a neonatal intensive care unit. Detailed records of events associated with airway management were kept after every intubation, in addition to clinical data. RESULTS: Eleven infants (4.8%) developed respiratory stridor after extubation which was treated with either systemic corticosteroids, racemic epinephrine and/or reintubation for respiratory failure. Four infants were submitted for bronchoscopy, mild subglottic stenosis with tracheal edema was found in 1 patient, granulation tissue and airway edema were noted in 3 infants. Traumatic intubation, prolonged ventilation, multiple intubations and bacterial colonization of the endotracheal tube were the factors associated with postextubation stridor. CONCLUSIONS: Subglottic stenosis is an infrequent complication of endotracheal intubation with current airway management of very-low-birth-weight infants. Less severe complications are still common, but they are usually amenable to clinical treatment. Bronchoscopy should be performed selectively only in infants with clinical evidence of airway obstruction after extubation.     

Effectively managing asthma in young and middle adulthood

Revised national guidelines for managing asthma in nonpregnant young adults and adults stress education for self-management and include provisions for stepped care. These guidelines also include education on asthma pathophysiology; measures to control exacerbations; medications available to treat the disease; use of inhalers, spacers, holding chambers and self-monitoring; and peak expiratory flow meters. Treatment is based on frequency of exacerbations and readings from the peak flow meter. The stepped-care approach means aggressively treating patients at a higher step than current signs and symptoms may warrant, to gain rapid control over these signs and symptoms. The new guidelines suggest that patients with intermittent asthma use inhaled, short-acting bronchodilators, whereas those with persistent asthma should begin with daily inhaled, antiinflammatory medicines. Once control is maintained for weeks or months, dosages can gradually be reduced to the minimum effective level.     

Studies on the stereoselective internal acyl migration of ketoprofen glucuronides using 13C labeling and nuclear magnetic resonance spectroscopy

BACKGROUND: To improve asthma disease management, the National Asthma Education Program (NAEP) Expert Panel published Guidelines for the Diagnosis and Management of Asthma in 1991. OBJECTIVES: To compare the current status of asthma disease management among patients in a large health maintenance organization with the NAEP guidelines and to identify the factors that may be associated with medical care (eg, emergency department visits and hospital admissions) and adherence to the guidelines. METHODS: Analyses of 1996 survey data from 5580 members with asthma (age range, 14 to 65 years) covered by a major health maintenance organization in California (Health Net). RESULTS: In general, adherence to NAEP guidelines was poor. Seventy-two percent of respondents with severe asthma reported having a steroid inhaler, and of those, only 54% used it daily. Only 26% of respondents reported having a peak flowmeter, and of those, only 16% used it daily. Age (older), duration of asthma (longer), increasing current severity of disease, and treatment by an asthma specialist correlated with daily use of inhaled steroids. Ethnicity (African American and Hispanic) correlated negatively with inhaled steroid use but positively with emergency department visits and hospital admissions for asthma. Increasing age and treatment by an asthma specialist were also identified as common factors significantly related to the daily use of a peak flowmeter and, interestingly, to overuse of beta2-agonist metered-dose inhalers. CONCLUSIONS: Although the NAEP guidelines were published 7 years ago, compliance with the guidelines was low. It was especially poor for use of preventive medication and routine peak-flow measurement. Furthermore, the results showed that asthma specialists provided more thorough care than did primary care physicians in treating patients with asthma. Combining the results of the regression analyses revealed that some of the variation in rates of emergency department visits and hospitalizations among some subpopulations can be explained by the underuse of preventive medication. This study serves the goal of documenting the quality of care and services currently provided to patients with asthma through a large health maintenance organization and provides baseline information that can be used to design and assess effective population-based asthma disease management intervention programs.     

Noninvasive positive-pressure ventilation for acute respiratory failure in a medical intensive care unit in Singapore

The main advantage of noninvasive ventilation over conventional mechanical ventilation is in the avoidance of endotracheal intubation and its related complications. Currently, the role of noninvasive ventilation in the management of patients with acute respiratory failure is still not firmly established. We conducted a prospective study to evaluate the efficacy of nasal positive pressure ventilation in patients with acute respiratory failure. Thirty-three consecutive patients with acute failure in whom intubation and mechanical ventilation were strongly considered were included in the study. They received ventilatory support by means of BiPAP ventilatory support system and nasal mask. Physical findings and laboratory measurements were documented before and at specific intervals after initiation of support. Eighty per cent (24/30) of patients were successfully supported. Successfully supported patients tolerated the device with improved gas exchange, hence avoiding endotracheal intubation. The mean duration of support was 19.2 hours. There were major associated complications, e.g. gastric distention or aspiration.     

Intracerebral bispecific ligand-antibody conjugate increases survival of animals bearing endogenously arising brain tumors

Noninvasive ventilation (NIV) is the provision of ventilatory support to a spontaneously breathing patient without endotracheal intubation. In this review, we detail concerns related to endotracheal intubation and summarize the physiologic effects and clinical application of NIV. We then address the use of NIV in 5 conditions of particular interest to the practitioner of emergency medicine: exacerbated chronic obstructive lung disease, severe asthma, patients who are not candidates for endotracheal intubation, pneumonia, and pulmonary edema.     

Intramuscular high-dose triamcinolone acetonide in the treatment of severe chronic asthma

We describe our experience with administering intramuscular triamcinolone acetonide to 22 steroid-dependent patients with asthma. These patients represent the minority of those with asthma whose disease is characterized by frequent emergency department visits, hospital admissions, and long-term dependency on oral corticosteroid therapy. The participants were randomly assigned to 2 treatment groups, one group receiving 120 mg of intramuscular triamcinolone acetonide, the second receiving 360 mg as a series of three 120-mg daily doses. We determined relative efficacy by comparing peak expiratory flow rates and incidents of emergency department visits, hospital admissions, and ventilatory failure of the study and during the 12 months before enrollment. Peak expiratory flow rates improved significantly in both groups. The mean (+/- standard deviation [SD]) monthly percentage of predicted peak expiratory flow on the study was 88.6 +/- 3.7% and 91.2 +/- 3.9% compared with 63 +/- 15.1% and 64 +/- 14.5% at entry in patients receiving 120 and 360 mg, respectively (P < 0.02). Patients receiving 120 mg required 8 hospital stays and 8 emergency department visits compared with 27 hospital stays and 72 emergency department visits in the previous year (P < 0.05). Patients receiving 360 mg required 5 hospital stays and 5 emergency department visits compared with 33 hospital stays and 34 emergency department visits in the previous year (P < 0.05). The average monthly interval (+/- SD) between exacerbations was 2.7 +/- 2.3 and 7.8 +/- 3.5 for patients receiving 120 mg and 360 mg, respectively. A total of 25 intubations was required in the previous year and only 1 during the study. The incidence of cushingoid facies, weight gain, and hypertension was reduced in both groups (P < 0.05). Total steroid use was reduced in both groups (P < 0.02). A dose of 360 mg produced a longer exacerbation-free period than 120 mg (P < 0.02).     

Intravascular ultrasound elastography

Asthma, a chronic disease of the respiratory tract, affects approximately five percent of the U.S. population, including almost five million children. Childhood asthma has been identified as the leading cause of school absences. This study was to examined efficacy of a school-based program to prevent exacerbation of asthma symptoms and manage asthma in school children using measured doses of an inhaled anti-inflammatory medication. The sample consisted of 22 African-American children in one inner-city elementary school in Dallas, Texas, ages 5-12 years with confirmed diagnoses of asthma. For three months, each child came to the school clinic two times per day for medication administration and measurement of respiratory peak flow rates. Data were collected for a number of variables including bronchodilator use, school absences, self-report of asthma symptoms, and number of visits to the physician. During the study, mean peak flow rates improved approximately 15%, and bronchodilator use decreased 66%. Improvement also was evident in several other areas.     

Noninvasive pressure support ventilation in COPD patients with postextubation hypercapnic respiratory insufficiency

Patients with chronic obstructive pulmonary disease (COPD) who have been intubated and mechanically ventilated may prove difficult to wean. Noninvasive ventilation may be used in an attempt to avoid new endotracheal intubation. The efficacy of administration of noninvasive pressure support ventilation was evaluated in 30 COPD patients with postextubation hypercapnic respiratory insufficiency, compared with 30 historically matched control patients who were treated conventionally. Patients were included in the study if, within 72 h postextubation, they presented with respiratory distress, defined as the combination of a respiratory frequency >25 breaths x min(-1), an increase in the arterial carbon dioxide tension (Pa,CO2) of at least 20% compared with the value measured after extubation, and a pH <7.35. Noninvasive pressure support ventilation was effective in correcting gas exchange abnormalities. The use of noninvasive ventilation significantly reduced the need for endotracheal intubation: 20 of the 30 patients (67%) in the control group required endotracheal intubation, compared with only six of the 30 patients (20%) in the noninvasive-ventilation group (p<0.001). In-hospital mortality was not significantly different between the two groups, but the mean duration of ventilatory assistance for the treatment of the postextubation distress, and the length of intensive care unit stay related to this event, were both significantly shortened by noninvasive ventilation (p<0.01). In conclusion, noninvasive ventilation may be used in the management of patients with chronic obstructive pulmonary disease and postextubation hypercapnic respiratory insufficiency.