Abstracts

Abstract

Bronchodilatation and Bronchoprotection in Asthmatic Preschool Children from Formoterol Administered by Mechanically Actuated Dry-Powder Inhaler and Spacer; Nielsen, K.G., Bisgaard, H.; Am. J. Resp. Crit. Care Med. 2001, 164, 256–259.

Background. Young asthmatic children have a specific need for more prolonged duration of bronchodilatation and bronchoprotection than is provided by intermittent therapy with short-acting beta-agonists. This is particularly true since young children are often under the care of others for large parts of the day. Inhaled Formoterol has a rapid onset of action, within a few minutes after inhalation, maximum effect at 30 minutes and sustained bronchodilatation and bronchoprotection for over 12 hours.

Objective. The objective was to evaluate the bronchodilatory and bronchoprotective efficacy of long-acting beta-agonist Formoterol, delivered as a dry-powder from a mechanically actuated dry-powder inhaler with a spacer.

Clinical Population. The clinical population included 12 asthmatic children, ages 2 to 5 years.

Clinical Protocol. Lung function was evaluated using specific airway conductance in a whole body plethysmograph. Cold dry air challenge with hyperventilation was used as a bronchial challenge, and the responsiveness was estimated as a change in the specific airway resistance. Bronchoprotective effect of Formoterol Turbohaler 9 mcg was compared with Salbutamol 200 mcg and placebo at 15 minutes, 4 hours, and 8 hours post dose in a randomized, double-blind, placebo-controlled crossover study. All treatments were delivered from a DPI “Turbohaler” actuated mechanically into a spacer.

Clinical Findings. Formoterol and Salbutamol produced similar and significant bronchodilatation at the first measurement, at 3 minutes post dose. Formoterol, however, offered persistent and stable bronchodilatation for at least 8 hours, while Salbutamol produced significant bronchodilatation for less than 4 hours. Formoterol produced significant bronchoprotection of 80% for at least 8 hours. The bronchoprotection from Salbutamol lasted less than 4 hours.

Conclusions. The conclusions of the authors were that Formoterol administered via dry-powder inhaler with a spacer in a single dose produced rapid (approximately 3 to 5 minutes onset) and sustained bronchodilatation (up to 12 hours) and clinically significant bronchoprotection for at least 8 hours in 2- to 5-year-old asthmatic children. This investigation further suggests that using a spacer is an effective way to deliver aerosol in young asthmatic children.

Reviewer's Comments. While Formoterol is exciting in terms of its pharmacodynamic properties, its delivery system is less than optimal when compared with ease of use of a Salmeterol discus haler. The introduction of a spacer here adds further mechanica1 obstacles, particularly for young children who are 2 to 5 years of age. However, the pharmacokinetic properties, i.e., the bronchoprotection and the bronchodilatation lasting up to 12 hours, is a useful modality when considering young children who are often in day care or nursery school for a large proportion of the day.

Christopher Randolph, M.D. Waterbury, CT

Abstract

Asthma Symptoms, Morbidity, and Anti-inflammatory Use in Inner-City Children; Warman, K.L., Silver, E.J., Stein, R.E.K.; Pediatrics 2001, 108, 277–282.

Background. Asthma is a leading cause of morbidity that has a disproportionate impact on inner-city children. For individuals with persistent asthma, defined by the NHLBI guidelines as symptoms occurring three or more days per week or three or more nights per month, the daily use of anti-inflammatory therapy is recommended. However, anti-inflammatory therapy remains underutilized, particularly, in the inner-city children with highest morbidity from asthma.

Objective. The objectives of the authors were to determine:

1. Whether there was a correlation between persistent asthma symptoms and acute care utilization and the frequency of acute exacerbations.

2. Whether children with persistent asthma were taking recommended daily anti-inflammatory therapy.

3. Whether anti-inflammatory medication use has any correlation with sociodemographic factors, the caretaker effectiveness, and the frequency of primary care visits and/or parameters of quality care of asthma.

Clinical Population. The clinical population included 219 parents/caretakers for children between 2 and 12 years old, who had been hospitalized with asthma in the inner-city medical centers between January 1995 and February 1996.

Design and Methods. The design of the study was a 64-item telephone survey administered to these caretakers between July 1996 and June 1997. Persistent asthma symptoms were evaluated by assessing the frequency of daily and nocturnal asthma symptoms over the last 4 weeks. The child's asthma severity was classified by the NHLBI guidelines. Asthma morbidity was defined by frequency of acute asthma exacerbations, emergency room visits, and hospitalizations. Daily anti-inflammatory medication use was compared by sociodemographic factors, i.e., insurance, public assistance, telephone availability, and steady telephone service. Caretaker self-efficacy was determined by education level. Care was also assessed by frequency of primary care visits and measures of quality asthma care, including written asthma action plan, a peak flow meter, and having a zippered plastic mattress cover for mite control. The caretaker self-efficacy was further evaluated using a seven-item scale, which evaluated their ability to handle an asthma crisis.

Results. The results of the study indicate that a majority of caretakers were mothers (92%) who were Hispanic (42%), Puerto Rican (17%), or African American (33%). Seventeen percent of children met the criteria for mild, intermittent asthma; 27% for mild, persistent asthma; and 56% for moderate to severe, persistent asthma. The mean age of the children in all three groups—mild, moderate, and severe—was 6 years. There were significantly more visits to the emergency room and asthma attacks in the last 6 months in those with moderate to severe asthma than those with mild, persistent asthma. The use of anti-inflammatory agents was noted in 35% of the 219 families, of these 83% gave cromolyn alone. Of the children with persistent asthma, 70, or 39%, were receiving daily anti-inflammatory medication and 61% were not. There was no difference in anti-inflammatory use based on the child's age, gender, or the caretakers race, educational level, insurance, or receipt of public assistance, and there was no difference between caretakers self-efficacy resources. Those who attended the outpatient clinic were more likely to be getting daily medication than those who went to a private doctor, the ED, or no usual place of care. The children averaged 3.1 visits to their clinician in the last 6 months, including 1.9 visits with asthma symptoms. The children on anti-inflammatory medications had more visits to their primary care provider than those who did not (4.5 versus 2.5) and more visits with asthma symptoms (3.2 versus 1.4). Correlation with use of daily anti-inflammatory medication was found in families that had a primary care provider and knew how to reach that individual. In addition, families that reported having a written action plan, a peak flow meter, or a zippered mattress cover were also twice as likely to report administering daily anti-inflammatory medication to their children.

Conclusions. The parents will hope to detect presence of more persistent symptoms and help guide therapy. The classifying of the asthma severity by the NAEPP or NHLBI guidelines is a clinically useful tool for asthma. Additional education work is essential to encourage the appropriate use of anti-inflammatory therapy in this inner-city population, particularly the increase of inhaled corticosteroid use in children for whom it is indicated with moderate to severe asthma.

Reviewer's Comments. This is a study that should be extended to other socioeconomic groups, particularly middle and upper middle class in suburban areas. The onus is on the physician and health care provider to be creative in developing additional programs to get families of children with moderate to severe asthma to take their medication regularly.

Christopher Randolph, M.D. Waterbury, CT

Abstract

The Risk of Hospitalization and Near-fatal and Fatal Asthma in Relation to the Perception of Dyspnea; Magadle, R., Berar-Yanay, N., Weiner, P.; Chest 2002, 121, 329–333.

Background. Fatal or near-fatal asthma episodes are a major consideration in asthma care. One of the principal objectives in managing individuals with asthma is the evaluation of patients at risk of having life-threatening episodes. It has been demonstrated that individuals who have near-fatal episodes have a blunted perception of dyspnea (POD).

Objective. The objective of this study is to quantify the POD in individuals with asthma and to relate POD to life-threatening episodes within a 24-month follow-up.

The clinical population was 113 consecutive asthmatic individuals with stable asthma who are attending an outpatient clinic in a medical center in Israel.

Methods. The POD was determined using the Borg scale breathing against an increasing load at intervals of 1 minute in order to achieve mouth pressures of up to 30 cm of water. The subjects rated their sensation of dyspnea. Pulmonary function testing was performed at baseline, and patients were followed every 3 months for approximately 24 months. Patients were encouraged to record peak flows, daily treatment, and document beta-agonist consumption.

Results. Seventeen patients had a high POD compared to normal subjects, while 67 patients had POD within the normal range and 29 patients with lower than normal POD. In individuals with low POD, there was a trend for higher age, higher female-to-male ratio, and a longer duration of asthma. The rate of severe asthma was higher in the low-POD group than in the normal-POD group but did not differ from the rate in the high-POD group. The mean daily beta-agonist consumption in the individuals with low POD was significantly lower (P < .01) than in the individuals with high POD, although the mean peak respiratory flow rate was lower in the low-POD group. During 2 years of evaluation, the individuals in the low-POD group had statistically significant more emergency room visits, hospitalizations, near-fatal asthma attacks, and death compared to the normal-POD and the high-POD groups.

Conclusions. The authors concluded reduced POD may predispose the subjects to life-threatening episodes of asthma.

Reviewer's Comments. Individuals with near-fatal asthma may have an apparently blunted POD, suggesting that malfunction of these defense mechanisms may relate to near-fatal asthma. These observations suggest that individuals who are prone to asthma fatalities have a poor perception of dyspnea, presumably explaining their low use of beta-agonists despite their frequent visits to the emergency room and hospital. The Borg scale may be useful in identifying individuals at risk for a fatal asthma attack. Individuals with low POD should be monitored very carefully and receive the progressive education in self-management.

Christopher Randolph, M.D. Waterbury, CT

Abstract

Heliox Therapy in Infants with Acute Bronchiolitis; Martinon-Torres, F., Rodriguez-Nunez, A., Martinon-Sanchez, J.M.; J. Pediatr. 2002, 109, 68–73.

Objective. The objective of the study was to evaluate the treatment outcome of inhaling a low-density gas mixture (heliox: 70% helium and 30% oxygen) in infants with bronchiolitis.

Design. The design of the study was a prospective interventional comparative program.

The setting of the study was the pediatric intensive care unit (ICU) in tertiary care teaching hospital.

The clinical population was 38 infants from age 1 month to 2 years, who were consecutively admitted to the ICU for treatment of moderate to severe acute respiratory syncytial virus bronchiolitis.

The first 19 patients were enlisted as the control group and were provided supportive care and nebulized epinephrine. The next 19 patients were given heliox therapy added through a non-rebreather reservoir face mask.

Respiratory distress scores, respiratory rate, heart rate, end-tidal CO₂ values were noted at baseline and at regular intervals. Each patient had demographic data collected: age, time elapsed from the start of symptoms to the pediatric ICU, length of stay in the pediatric ICU, and duration of heliox therapy. The primary outcomes were the decline in clinical scores in pediatric ICU and length of stay.

Clinical Findings. The clinical findings at baseline for both the heliox and control groups were similar. The clinical score, heart rate, respiratory rate, and O₂ saturation improved during the study in both groups.

However, following 1 hour, the improvement in clinical scores was significantly improved in the heliox group when compared with the control group. These differences remained significant until the end of the observation period, with a total average decline in the score of 4.2 points in the heliox group when compared with 2.5 points in the control group. Heart and respiratory rate were also significantly lower in the heliox group when compared with the control group after 1 hour and remained so throughout the rest of the period. However, no change was noted in the saturation of O₂ between the two groups or the end-tidal CO₂. The pediatric ICU length of stay was significantly less in the heliox group (3.5 + 1.1 days) compared to the control group (5.4 + 1–1.6 days).

Conclusions. The conclusion of the authors is that for infants with moderate to severe respiratory syncytial virus bronchiolitis, heliox therapy appears to improve their clinical respiratory status, as indicated by marked enhancement in their clinical scores and a decline in the associated tachycardia and tachypnea. This improvement occurred within the first hour of the administration of heliox and continued as long as heliox therapy continued. The pediatric ICU length of stay was reduced as well in heliox patients.

Reviewer's Comments. Given the minimal available approaches to treatment of acute bronchiolitis presently, which is largely supportive, heliox therapy is a welcome addition to the setting of the pediatric ICU for moderate to severe respiratory syncytial virus bronchiolitis.

The heliox itself, while improving the respiratory outcome of infants with acute bronchiolitis, is safe, noninvasive, and simple in its utilization; however, cost-benefit analysis would be useful to determine its place in the long-term treatment of bronchiolitis. This study is limited by its sample size and the use of changes in the clinical score, which are subjective, as a primary outcome.

Christopher Randolph, M.D. Waterbury, CT