Patients In Status Asthmaticus Research Articles

Inhaled Volatiles for Status Asthmaticus, Epilepsy, and Difficult Sedation in Adult ICU and PICU: A Systematic Review.

Inhaled volatile anesthetics support management of status asthmaticus (SA), status epilepticus (SE), and difficult sedation (DS). This study aimed to evaluate the effectiveness, safety, and feasibility of using inhaled anesthetics for SA, SE, and DS in adult ICU and PICU patients. MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Primary literature search that reported the use of inhaled anesthetics in ventilated patients with SA, SE, and DS from 1970 to 2021. Study data points were extracted by two authors independently. Quality assessment was performed using the Joanna Briggs Institute appraisal tool for case studies/series, Newcastle criteria for cohort/case-control studies, and risk-of-bias framework for clinical trials. Primary outcome was volatile efficacy in improving predefined clinical or physiologic endpoints. Secondary outcomes were adverse events and delivery logistics. From 4281 screened studies, the number of included studies/patients across diagnoses and patient groups were: SA (adult: 38/121, pediatric: 28/142), SE (adult: 18/37, pediatric: 5/10), and DS (adult: 21/355, pediatric: 10/90). Quality of evidence was low, consisting mainly of case reports and series. Clinical and physiologic improvement was seen within 1-2 hours of initiating volatiles, with variable efficacy across diagnoses and patient groups: SA (adult: 89-95%, pediatric: 80-97%), SE (adults: 54-100%, pediatric: 60-100%), and DS (adults: 60-90%, pediatric: 62-90%). Most common adverse events were cardiovascular, that is, hypotension and arrhythmias. Inhaled sedatives were commonly delivered using anesthesia machines for SA/SE and miniature vaporizers for DS. Few (10%) of studies reported required non-ICU personnel, and only 16% had ICU volatile delivery protocol. Volatile anesthetics may provide effective treatment in patients with SA, SE, and DS scenarios but the quality of evidence is low. Higher-quality powered prospective studies of the efficacy and safety of using volatile anesthetics to manage SA, SE, and DS patients are required. Education regarding inhaled anesthetics and the protocolization of their use is needed.

A CASE OF NEAR-FATAL ASTHMA EXACERBATION

A CASE OF NEAR-FATAL ASTHMA EXACERBATION

Reducing Avoidable Transfer Delays in the Pediatric Intensive Care Unit for Status Asthmaticus Patients.

Introduction:Status asthmaticus (acute severe asthma) is one of the most common reasons for Pediatric Intensive Care Unit (PICU) admission. Accordingly, ensuring optimal throughput for patients admitted with status asthmaticus is essential for optimizing PICU capacity. Few studies specifically address effective methods to reduce delays related to PICU discharge. This project aimed to identify and reduce avoidable delays in PICU discharge for status asthmaticus patients.Methods:This quality improvement project focused on reducing transfer delays for status asthmaticus patients admitted to the PICU at a freestanding academic children’s hospital. We standardized the transfer criteria, identified barriers to an efficient transfer, and implemented multidisciplinary interventions. The primary aim was to decrease the average duration from fulfilling the transfer criteria to PICU discharge by 15% from the baseline within 8 months of implementation. The balancing measure was readmissions to the PICU for asthma exacerbations within 24 hours from PICU discharge.Results:The analysis included 623 patients. Following interventions, the time from fulfilling transfer criteria to PICU discharge decreased from 9.8 hours to 6.8 hours, a 30.6% reduction from baseline. Improvements were sustained for 6 months. In the preintervention group, three patients were readmitted to the PICU within 24 hours of transferring out of the PICU, but no patient was readmitted during the postintervention period.Conclusions:Standardizing transfer criteria and implementing multidisciplinary strategies can reduce avoidable PICU discharge delays for patients with status asthmaticus. The application of a similar approach could potentially reduce avoidable delays for other conditions in the PICU.

Safety of prolonged magnesium sulfate infusions during treatment for severe pediatric status asthmaticus.

Magnesium sulfate (Mg) is one of several "second-tier" therapies for treating severe status asthmaticus. Pediatric reports primarily describe bolus use with limited data regarding prolonged infusions. We sought to describe the safety of prolonged Mg infusions during therapy of status asthmaticus in critically ill children. Single center, retrospective study. Thirty-four-bed tertiary level medical/surgical/cardiac surgical pediatric intensive care unit. Pediatric patients 2 to 18 years of age admitted with status asthmaticus receiving Mg infusion for more than 24 hours. None. A total of 154 children received Mg infusions for a median of 53.4 hours (interquartile range = 36.6-74.8). The most common adverse event (AE) was hypotension (48.1%), almost exclusively diastolic (94%), and was mostly limited to 1 blood pressure measurement (78%). 2.9% of events required intervention (fluids, decrease Mg infusion). Other AEs included nausea/emesis (22.7%), transient weakness (14.9%), and flushing (6.5%). Five patients experienced serious AEs including hypotonia (n = 1), escalation to continuous or bilevel positive airway pressure (n = 3), and sedation (n = 1), all attributed to progression of underlying medical disease. No patient required endotracheal intubation. Supratherapeutic levels (>6 mg/dL) were uncommon (2%) and were not more likely to be associated with AEs. Most (81%) patients were therapeutic by the 2nd Mg level check. Prolonged Mg infusions were well tolerated in pediatric status asthmaticus patients. While diastolic hypotension was not uncommon, rarely were interventions deemed necessary. No serious AEs were attributed to Mg. Toxicity was uncommon suggesting that Mg levels could potentially be checked less frequently than historically reported.

Implementing a Respiratory Therapist-Driven Continuous Albuterol Weaning Protocol in the Pediatric ICU.

Status asthmaticus is one of the most frequent admission diagnoses in the pediatric ICU (PICU). Collaboration between respiratory therapists (RTs) and physicians may help efficiently deliver care to a patient in status asthmaticus. The Pediatric Asthma Severity Score (PASS) is a measure of severity of a patient's asthma exacerbation at a point in time. The aim of this quality improvement initiative was to establish an RT-driven continuous albuterol weaning protocol using the PASS score. We hypothesized that this would decrease the duration of continuous albuterol without increasing adverse events. This was a single-center implementation study in the PICU of a quaternary care children's hospital. Patients with a diagnosis of status asthmaticus who met criteria on continuous albuterol between September 2015 and September 2017 were included. An interdisciplinary team established the protocol, order sets, documentation, and education for involved staff. Qualifying subjects were assessed by an RT per protocol and assigned a PASS score, and the albuterol dose was adjusted on the basis of the PASS score. We compared 104 subjects studied before the implementation of this protocol (September 2015 to August 2016) to 117 subjects after the implementation of this protocol (September 2016 to October 2017). Median (interquartile range) duration of continuous albuterol in the PICU post-implementation was unchanged compared to pre-implementation: 12.1 (7.2-21.0) h versus 11.1 (6-19) h (P = .22). Median PICU length of stay was also unchanged post-implementation compared to pre-implementation: 19.5 (14.3-29.7) h versus 23.2 (15.2-31.3) h (P = .16). Using control charts, these processes were stable. There was no difference in adverse events. An interprofessionally-developed, RT-driven continuous albuterol weaning protocol can be implemented without negatively impacting duration of continuous albuterol or PICU length of stay and without increasing adverse events.

NATIONAL OUTCOMES OF STATUS ASTHMATICUS AMONG THE ELDERLY

SESSION TITLE: Critical Care 2 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Asthma is an unrecognized entity in the elderly with a prevalence of 13%. Acute asthma exacerbation (AAE) in this population presents a significant risk of morbidity and mortality. Status asthmaticus (SA) represents the most severe presentation of this disease, in which asthma attacks occur continuously without remission. Outcomes of AAE and SA in the elderly are not well studied. We sought to investigate the impact of SA among elderly patients in a large national dataset. METHODS: The National Inpatient Sample (NIS) was investigated for geriatric patients admitted with SA and AAE between 2009 and 2014. Demographic and clinical characteristics, including age, sex, race, income groups, comorbidity, and hospital types were compared between groups. We then compared across clinical outcomes of interest, including use of non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV), prolonged IMV > 96 hours, in-hospital mortality and discharge to home. All estimates utilized appropriate complex survey methods, such that estimates were nationally representative. Significant differences between groups were tested using Rao-Scott Chi-Square. RESULTS: There were 475,770 weighted discharges for asthma exacerbation over the study period, of which 15,318 (3.2%) were SA. Overall, female sex (72.3%), was predominant in our cohort with multiple comorbidities (78.3%), and highest prevalence in the winter (29.3%) and spring (27.0%) months. Patients with SA tended to be slightly younger than those with AAE (AAE mean 75.9 y vs SA mean 74.7 y, p<0.0001) and had a longer length of stay (AAE mean 4.6 d vs SA 5.5 d, p<0.0001). Although there were similar rates of NIMV use (AAE 4.5% vs SA 5.4%, p = 0.05), there was a more than two-fold difference in the rate of IMV (AAE 1.5% vs SA 4.4%, p<0.0001). Despite this, among patient who did receive IMV, there were no significant differences in prolonged IMV >96 hours (AAE 34.3% of IMV vs SA 31.5% of IMV, p=0.52). Furthermore, though there were similar rates of in-hospital mortality in patients admitted with SA (AAE 0.9% vs SA 1.2%, p = 0.06), SA patients were significantly more likely to be discharged to home without services (AAE 65.9% vs SA 71.4%, p <0.0001). CONCLUSIONS: Patients admitted with SA were more likely to receive IMV than their AAE counterparts, yet were more frequently discharged home without services. SA in the elderly is associated with a high mortality and warrants aggressive interventions. Clinicians should be aware and have a low threshold for ventilator support when appropriate to avoid adverse clinical outcomes. CLINICAL IMPLICATIONS: There is need to keep a low threshold for ventilator support, NIMV or IMV in the elderly with SA. DISCLOSURES: No relevant relationships by Raymonde Jean, source=Web Response No relevant relationships by Raymond Jean, source=Web Response No relevant relationships by Sathish Pondaiah, source=Web Response No relevant relationships by Bertin Salguero, source=Web Response No relevant relationships by Fernando Vazquez de Lara, source=Web Response

Characteristics and outcomes of treatment in status asthmaticus patients at emergency department.

The characteristics and treatment outcomes of status asthmaticus patients in emergency department (ED) have not been described previously especially in Thailand. To describe the characteristics, treatment outcomes and factors associated with status asthmaticus in Thai patients presenting to a single center ED. A prospective observational study was performed at Thammasat University hospital, Thailand. The data collected included demographics, asthma history and control, previous ED attendances and hospital admissions, presenting clinical, laboratory and radiographic features, treatments given, and outcomes. Multivariable regression was used to determine independent factors associated with status asthmaticus. Over one year (2015-16), 209 patients were recruited, aged 6 - 54 years (median 33 y), of whom 145 (69.3%) had status asthmaticus. The factors associated with status asthmaticus were: (i) age > 60 y, (ii) presence of a comorbidity, (iii) having uncontrolled asthma, (iv) hospitalizations or visits to the ED in the last year, and (v) using > 1 metered dose inhaler canister per month. Status asthmaticus patients were significantly less likely to speak in sentences (p=0.001) and more likely to have poor air entry and chest wall retraction (p<0.0001), an abnormal chest X ray (p=0.011), receive magnesium sulphate and be admitted into hospital (p<0.0001). No patients died. Status asthmaticus was common in this cohort of patients in our setting. Our findings are consistent with previous studies and underscore the need for better patient management.

Bronchoscopy as a salvage therapy in a mechanically ventilated status asthmaticus patient: A case report

A 23-year-old male patient presented with acute exacerbation of asthma with type 2 respiratory failure. He was mechanically ventilated and started on intensive medical therapy including nebulization with β2 agonists and antimuscarinic drugs, steroids, antibiotics and magnesium sulphate as per standard protocol. As there was no response to the abovementioned line of treatment, other nonstandard therapies such as intramuscular adrenaline and ketamine were also tried but to no avail. After a meticulous literature search, bronchoscopy was planned to look for any alternative diagnoses as well as to perform bronchial toileting. The patient showed dramatic improvement after the procedure, was subsequently extubated and discharged in stable condition. This case essays the significant role of bronchoscopy in refractory status asthmaticus patients, discusses the pathophysiological mechanisms addressed by bronchoscopic toileting and, furthermore, reviews the contemporary literature for evidence in its favour.

Failure of noninvasive ventilation in adult patients with acute asthma exacerbation.

Failure of noninvasive ventilation in adult patients with acute asthma exacerbation.

Emergency treatment of status asthmaticus with enoximone

This report describes the treatment of eight patients with status asthmaticus, six of whom were already maximally treated. They were consequently treated with enoximone, a selective phosphodiesterase III inhibitor, in their refractory phase. Bronchodilatation in these patients was immediate. No side-effects were observed. Enoximone appears to be a valuable addition to the treatment of status asthmaticus. I.V. administration bypasses inhalation incapability in severe asthma. It is likely to reduce or altogether prevent the need for resorting to secondary or tertiary high-tech therapy such as mechanical ventilation or anaesthetics, thus avoiding complications, as well as for transfers to specialized intensive care units. Not only do these aspects enable substantial cost savings, but they also may spare the patient a lot of anguish and a prolonged recovery.

Hospitalization rate and 30-day mortality among patients with status asthmaticus in Denmark: a 16-year nationwide population-based cohort study

ObjectiveCurrent data on hospitalization and prognosis of acute asthma and status asthmaticus are inconclusive. We aim to analyze the rate of first-time hospitalizations for status asthmaticus among patients of all ages, the proportion admitted to intensive care units (ICU), and the 30-day mortality over a 16-year period.MethodsIn this population-based cohort study, we used medical registries to identify all first-time status asthmaticus hospitalizations in Denmark from 1996 through 2011. Data on comorbidities were also obtained. We computed yearly hospitalization rates overall and by gender and age groups, and estimated the proportion requiring ICU admission. We estimated 30-day age- and gender-standardized mortality. We examined potential misclassification from acute exacerbation of chronic obstructive pulmonary disease (COPD) by excluding patients with preexisting or concurrent COPD.ResultsOf the 5,001 patients identified with a first-time status asthmaticus hospitalization, 50.5% were male, 40.3% were <15 years old, and 12.4% had comorbidity. The hospitalization rate increased from 48.0 per 1,000,000 person-years (PY) (95% confidence interval [CI]: 45.1–51.1 PY) during 1996–1999 to 70.1 per 1,000,000 PY (95% CI: 66.7–73.7 PY) during 2008–2011. This may be explained by an increased hospitalization rate of children. The standardized 30-day mortality risk declined from 3.3% (95% CI: 2.5%–4.1%) in 1996–1999 to 1.5% (95% CI: 0.9%–2.1%) in 2008–2011. During 2005–2011, 10.1% of status asthmaticus patients were admitted to the ICU. Hospitalization rates and mortality risk decreased by excluding 939 patients also registered with COPD, but overall temporal changes did not change.ConclusionFrom 1996 to 2011, status asthmaticus hospitalization rate increased but remained below 100 hospitalizations per 1,000,000 PY. Thirty-day mortality risk was halved to less than 2%.

BiPAP for treating moderate and severe asthma exacerbations in a PED

BiPAP utilization for the treatment of severe refractory status asthmaticus patients has become an accepted therapy but is not well described for moderate exacerbations. We sought to analyze outcomes from our BiPAP quality database for children presenting in status asthmaticus at varying levels of severity.

Tracheobronchial mycosis in a retrospective case-series study of five status asthmaticus patients

The etiology of status asthmaticus (SA), a complication of severe asthma, is unknown. Fungal exposure, as measured by fungal atopy, is a major risk factor for developing asthma, but the relationship of fungi in SA per se has not previously been reported. In this five patient retrospective case series study, lower respiratory tract cultures were performed on bronchoalveolar lavage or tracheal aspirate fluid, comparing standard clinical laboratory cultures with a specialized technique in which respiratory mucus was removed prior to culture. We show that mucolytic treatment allows an increased detection of fungal growth, especially yeast, from the lower airways of all SA patients. We also demonstrate that inhalation of the yeast Candida albicans readily induces asthma-like disease in mice. Our observations suggest that SA may represent a fungal infectious process, and support additional prospective studies utilizing anti-fungal therapy to supplement conventional therapy, broad-spectrum antibiotics and high-dose glucocorticoids, which can promote fungal overgrowth.

The Critically Ill Asthmatic—from ICU to Discharge

Status asthmaticus (SA) is defined as an acute, severe asthma exacerbation that does not respond readily to initial intensive therapy, while near-fatal asthma (NFA) refers loosely to a status asthmaticus attack that progresses to respiratory failure. The in-hospital mortality rate for all asthmatics is between 1% to 5%, but for critically ill asthmatics that require intubation the mortality rate is between 10% to 25% primarily from anoxia and cardiopulmonary arrest. Timely evaluation and treatment in the clinic, emergency room, or ultimately the intensive care unit (ICU) can prevent the morbidity and mortality associated with respiratory failure. Fatal asthma occurs from cardiopulmonary arrest, cerebral anoxia, or a complication of treatments, e.g., barotraumas, and ventilator-associated pneumonia. Mortality is highest in African-Americans, Puerto Rican-Americans, Cuban-Americans, women, and persons aged ≥ 65 years. Critical care physicians or intensivists must be skilled in managing the critically ill asthmatics with respiratory failure and knowledgeable about the few but potentially serious complications associated with mechanical ventilation. Bronchodilator and anti-inflammatory medications remain the standard therapies for managing SA and NFA patients in the ICU. NFA patients on mechanical ventilation require modes that allow for prolonged expiratory time and reverse the dynamic hyperinflation associated with the attack. Several adjuncts to mechanical ventilation, including heliox, general anesthesia, and extra-corporeal carbon dioxide removal, can be used as life-saving measures in extreme cases. Coordination of discharge and follow-up care can safely reduce the length of hospital stay and prevent future attacks of status asthmaticus.

8-Isoprostane in the exhaled breath condensate of children hospitalized for status asthmaticus

To evaluate the safety and feasibility of exhaled breath condensate (EBC) collection in children recovering from status asthmaticus (SA) in a pediatric intensive care unit (PICU); and to investigate whether 8-isoprostane (8-Iso) could be detected in the EBC of these children and to compare its concentration with that in the EBC collected from healthy children. Prospective study. Multidisciplinary PICU in a teaching hospital. Sixteen consecutive patients (7-18 yrs of age) with SA and 16 age- and sex-matched controls. The Wood clinical asthma score and the pulmonary index were used to assess the clinical severity of patients with SA upon admission to the PICU. EBC samples were collected within 24 hrs of admission to the PICU and were analyzed for the concentration of 8-Iso. Data are presented as mean ± sd values. There were no differences in age (12 ± 3.3 yrs vs.12 ± 2 yrs, p > .05) or sex (n = 10 males and n = 6 females in each group), between SA patients and controls. All patients with SA and the controls completed the EBC collection without complications. There was no statistically significant difference in the pulmonary index (3.2 ± 2.7 vs. 3.1 ± 2.8, p 0.9) post collection of EBC compared with the baseline values. There was a statistically significant correlation between Wood score and pulmonary index at the time of admission to the PICU in children with SA (r = .7, p < .01). The concentration of 8-Iso was significantly higher in the EBC of children with SA compared with controls (14.3 ± 1.8 pg/mL vs. 5.2 ± 0.7 pg/mL, p < .001). The correlation between the concentration 8-Iso and either the pulmonary index or Wood score at the time admission to the PICU was not statistically significant. EBC collection is well tolerated by children aged 7-18 yrs who are recovering from SA in a PICU. 8-Iso is elevated in the EBC from children with SA and may provide insight into the biochemical changes of oxidative stress in children in this clinical setting.

Continuous Levalbuterol and Albuterol Comparable

Source: Andrews T, McGintee E, Mittal MK, et al. High-dose continuous nebulized levalbuterol for pediatric status asthmaticus: a randomized trial. J Pediatr. 2009;155(2):205–210; doi:10.1016/j. jpeds.2009.01.073Investigators from the Children’s Hospital of Philadelphia performed a randomized, double-blind, controlled trial comparing continuous administration of nebulized albuterol 20 mg/hr or levalbuterol ([R]-albuterol) 10 mg/hr to children aged 6 to 18 years admitted to the hospital with status asthmaticus. Study eligibility required participants to have an established diagnosis of asthma. Patients in status asthmaticus who did not show a substantial clinical improvement with standardized care in the emergency department, including three 5-mg doses of nebulized albuterol, two 500-mcg doses of ipratropium bromide, and a 2 mg/kg dose (to a maximum of 60 mg) of either oral prednisolone or parenteral methylprednisolone, were eligible for enrollment. In addition to the study medications, enrolled children received oral prednisone/prednisolone or intravenous methylprednisolone and they continued at home doses of inhaled corticosteroids. Patient response to treatment as measured by the Pediatric Asthma Severity Score1 was used to wean asthma medications. The primary outcome was duration of continuous nebulized β-agonist therapy. Blood samples were taken from the first 40 children to assess serum concentration of (S)- and (R)-albuterol, blood glucose, and potassium.One hundred forty-three patients were approached for potential enrollment and 81, with a mean age of 10 years, were enrolled. More than 90% were African American. The median duration of continuous inhaled β-agonists was not significantly different, 18.3 hours for albuterol and 16 hours for levalbuterol. The median time to be ready for discharge did not differ significantly (45 hours vs 46 hours) between the groups. There were no differences in mean or maximum heart rate, mean glucose, or serum potassium concentrations between groups. (S)-albuterol concentrations were significantly greater in the albuterol group at all time points measured; however, (R)-albuterol concentrations were similar in both groups.The authors conclude that both continuous albuterol and levalbuterol treatments were well tolerated in patients who had failed initial albuterol therapy and had similar efficacy.Dr Ibsen has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Asthma is a leading cause of hospitalization of children, and costs related to asthma care, particularly those associated with emergency and hospital-based treatment, are increasing. Systemic corticosteroids combined with frequent repeated administration of short-acting β-adrenergic agonists remain the basis of most acute asthma treatments. Continuous administration of β-agonists, utilized in severely ill patients, results in increased bronchodilation compared with intermittent treatment.2Albuterol is available as a racemic mixture of (R)-albuterol and (S)-albuterol. (R)-albuterol is the therapeutically active form with significantly higher affinity for β2-agonist receptors, and produces bronchodilation as well as tachycardia and tremor. (S)-albuterol has been shown in vitro to promote inflammatory cell and smooth muscle proliferation, to increase intracellular calcium, and to enhance airway hyper-responsiveness. The commercial availability of pure (R)-albuterol, levalbuterol, has led to evaluation of the therapeutically active form. However, studies comparing levalbuterol with racemic albuterol report inconsistent findings.3,4Levalbuterol is substantially more expensive than racemic albuterol so it is worth understanding if there is clinical benefit to its use. The study institution had a well-defined asthma protocol that included continuous albuterol for approximately 40% of hospitalized patients, and care and progression of patients in the study continued to be directed by the standard inpatient asthma protocol.The authors concluded that there were no significant differences in either clinical effectiveness or adverse effects between continuous levalbuterol and racemic albuterol. Interestingly, nine patients (11% of those enrolled) required re-institution of continuous therapy after weaning to intermittent therapy, six in the racemic group and three in the levalbuterol group. Although the numbers are small, this may represent an effect of the long-acting (S)-albuterol on airway responsiveness.This study expands our understanding of the place for levalbuterol in the treatment of severe pediatric asthma. There appears to be no benefit for the routine use of continuous levalbuterol over albuterol in the treatment of severe acute asthma. Because all patients in the study were exposed to (S)-albuterol prior to study entry, further investigation may yet demonstrate some benefit to using levalbuterol as initial therapy for severe acute asthma.

Efficacy of Inhaled Anticholinergics and Anesthesia in Treatment of a Patient in Status Asthmaticus

Despite better knowledge of the pathophysiology of asthma and the improved availability of pharmacological treatment, there are still some patients who require more intensive medical therapy and me...

CC chemokines and interleukin-5 in bronchial lavage fluid from patients with status asthmaticus. Potential implication in eosinophil recruitment.

In status asthmaticus (SA), severe bronchial inflammation is associated with acute respiratory failure. Neutrophils are the prominent cells found in bronchi from SA patients, but eosinophils are also recruited within the first 48 h after the beginning of mechanical ventilation (MV). Interleukin (IL)-5 and CC chemokines have been directly implicated in the pathophysiology of allergic asthma. However, their involvement in SA had not been determined. The aim of this study was to evaluate the production of CC chemokines and of IL-5 in airways from ventilated patients with SA as compared with mild asthma (A), and to assess the role of these mediators in eosinophil recruitment. We measured levels of the chemokines monocyte chemotactic proteins (MCPs)-1 and -3; regulated on activation, normal T-cell expressed and secreted (RANTES); macrophage inflammatory peptide (MIP)-1alpha; and eotaxin; and of the cytokine IL-5 in bronchial lavage fluid (BLF) from 10 SA patients, four patients without respiratory disease but undergoing ventilation (V) who were receiving MV, 11 patients with A, and eight healthy volunteers (C). We further evaluated in vitro eosinophil chemotactic activity of BLF from the various groups. Levels of MCP-1, MIP-1alpha, RANTES, and IL-5 were significantly higher in the SA than in the V, A, and C groups. MCP-3 and eotaxin values were not significantly different in the SA and other groups; however, their levels, as well as those of MIP-1alpha, RANTES, and IL-5 correlated with eosinophil influx. Eosinophil chemotactic activity in BLF was increased in asthmatic subjects (A and SA groups) as compared with the other groups, and in SA patients as compared with A patients. Addition of neutralizing anti-IL-5, anti-MCP-3, anti-eotaxin, and anti-RANTES antibodies significantly inhibited the eosinophil chemotactic activity as compared with that of native BLF. This study shows that the levels of various CC chemokines and IL-5 are increased in airways of SA patients, and are potentially involved in eosinophil recruitment.

Dose-Response Characteristics of Nebulized Albuterol in the Treatment of Acutely Ill, Hospitalized Asthmatics

We investigated the bronchodilator dose-response to nebulized albuterol and the dose of albuterol which produces maximal bronchodilation in the acutely ill, hospitalized asthmatic. Consecutively admitted patients from the emergency room in status asthmaticus who fulfilled the inclusion criteria (age <41 years old and <12 pack-years of smoking) were studied. Albuterol was administered by nebulizer (Puritan-Bennett Raindrop) in repeated 2.5-mg treatments up to a total dose of 10 mg and the bronchodilator response was measured by a computerized spirometer. Twenty-two patients were studied. Baseline spirometry showed a (mean ± SE) forced expiratory volume in 1 sec (FEV1) of 1.26 ± 0.14 L (42 ± 4.0% predicted), which increased significantly (p < 0.05) during albuterol titration to a maximum FEV1 of 1.70 ± 0.19 L (57 ± 5% of predicted). After cumulative doses of 2.5, 5.0, 7.5, and 10.0 mg of nebulized albuterol, 27%, 45%, 72%, and 77% of patients, respectively, attained maximum bron- chodilation. The remaining 23% of patients did not respond to doses up to 10 mg of albuterol. The maximum FEV1, response to albuterol did not correlate with the initial severity of airflow obstruction (r = 0.36, p > 0.05). Pulse rate and arterial oxygen saturation were not significantly affected by nebulized albuterol up to a total dose of 10 mg. No arrhythmias were noted. In summary, most hospitalized asthmatics (72%) required a cumulative dose of 7.5 mg of nebulized albuterol to achieve maximum bronchodilation and a large fraction (50%) required higher albuterol doses than the standard 2.5 mg. The broncho-dilatory response to nebulized albuterol varied widely among patients in status asthmaticus and could not be predicted from the initial severity of airflow obstruction. Because side effects were minimal, it would be reasonable to use 7.5 mg of nebulized albuterol as initial therapy. Alternatively, dose-response titration with albuterol would be advantageous.

Measurement of peptidoleukotrienes in biological fluids

Samples of human bronchoalveolar lavage fluid (BALF) and urine were utilized to demonstrate methods for quantitation and validation of leukotrienes (LTs). These methods utilize an enzyme immunoassay (EIA) that uses commercially available reagents, the antibody recognizing LTC4, LTD4, LTE4, and N-acetyl LTE4. BALF containing epithelial lining fluid was collected from atopic asthmatics both before and 5 min after the subjects had been challenged with a local instillation of allergen into the airways. BALF samples collected without allergen challenge had low levels of immunoreactive LTs, whereas samples collected after allergen were markedly elevated. After high-performance liquid chromatography (HPLC) separation of LTs, EIA revealed the presence of LTC4. The identity was validated by incubating LTC4 with a bovine gamma-glutamyl transpeptidase with dipeptidase activity that converted added [3H]-LTC4 as well as LTC4 immunoreactivity to LTE4. Urine samples collected from six healthy volunteers, one patient with adult respiratory distress syndrome (ARDS), and three patients in status asthmaticus were also analyzed for LTs. After HPLC separation of LTs and quantitation by EIA, urine samples from healthy subjects were found to have low but measurable LTE4. In contrast, the urine samples from the patients in status asthmaticus and from the ARDS patient had large elevations of LTE4 levels compared with healthy subjects. When the HPLC fractions containing [3H]LTE4 and LT immunoreactivity in the ARDS sample were treated with acetic anhydride, HPLC analysis indicated that both radiolabel and immunoreactivity now eluted at the retention time of N-acetyl LTE4, the derivatized product of LTE4. The methods described are relatively easy and can be used to measure and validate the existence of peptidoleukotrienes in biological samples.