Articles

ABSTRACT

BACKGROUND: Asthma management guidelines recommend patients with persistent asthma use asthma controller therapy in addition to as-needed short-acting beta-agonist therapy to improve symptom control, maintain pulmonary function, and decrease exacerbations. This study compared 2 asthma controllers, inhaled fluticasone and oral montelukast, with respect to clinical efficacy, patient preference, asthma-specific quality of life, and safety.
POPULATION STUDIED: The patients in this study were men and women aged 15 years and older with asthma recruited from multiple centers across the United States. Nonsmoking patients were included with a forced expiratory volume in 1 second (FEV 1 ) of 50% to 80% of predicted that reversed by at least 15% with bronchodilator use. Patients were then eligible for randomization if, after an 8- to 14-day run-in period, their FEV 1 remained within 15% of initial values, they used albuterol at least 6 of the last 7 days, and they had asthma symptom scores of 2 (on a 0 to 5 scale) for at least 4 of the last 7 days.
STUDY DESIGN AND VALIDITY: This study was a double-blinded, randomized trial sponsored by the makers of fluticasone. Patients meeting initial inclusion criteria underwent an 8- to 14-day run-in period in which only short-acting beta-agonist use was allowed. Patients were then randomized to 1 of 2 treatment groups if they met the secondary inclusion criteria. Personal communication with the lead author confirmed that allocation assignment was concealed. Patients received either fluticasone 88 μg twice daily via metered dose inhaler (MDI) and montelukast placebo, or montelukast 10 mg daily with a placebo MDI. Patients kept daily records and had clinical evaluations at regular intervals for 24 weeks. Seventy-six percent of the patients completed the study.
OUTCOMES MEASURED: The primary outcome was percent change in FEV 1 . Other outcomes included peak flow rate, symptom-free days, daily albuterol use, asthma symptom scores, asthma quality-of-life scores, and patient-rated satisfaction with treatment. Safety was also assessed by reports of clinical adverse events and number of asthma exacerbations.
RESULTS: Using an intent-to-treat analysis, the fluticasone group had a significantly greater sustained change in FEV 1 (22% vs 14%; P < .001). Significant differences were noted after just 2 weeks of treatment. Significant differences favoring fluticasone were also found in all secondary outcomes including the patient-oriented outcomes of change in asthma symptom scores (–0.91 vs –0.57; P < .001), asthma quality-of-life scores (1.3 vs 1.0; P = .004), and patient-rated satisfaction with treatment (83% of fluticasone patients satisfied vs 66% of montelukast patients satisfied; P < .001). No differences were noted in overall incidence of adverse events between treatment groups, but significantly more fluticasone-treated patients reported hoarseness (9 vs 0; P = .002) and oral pharyngeal candidiasis (8 vs 0; P = .008). The incidence of asthma exacerbations was similar (19 fluticasone-treated patients vs 21 montelukast-treated patients).

ABSTRACT

BACKGROUND: Asthma management guidelines recommend patients with persistent asthma use asthma controller therapy in addition to as-needed short-acting beta-agonist therapy to improve symptom control, maintain pulmonary function, and decrease exacerbations. This study compared 2 asthma controllers, inhaled fluticasone and oral montelukast, with respect to clinical efficacy, patient preference, asthma-specific quality of life, and safety.
POPULATION STUDIED: The patients in this study were men and women aged 15 years and older with asthma recruited from multiple centers across the United States. Nonsmoking patients were included with a forced expiratory volume in 1 second (FEV 1 ) of 50% to 80% of predicted that reversed by at least 15% with bronchodilator use. Patients were then eligible for randomization if, after an 8- to 14-day run-in period, their FEV 1 remained within 15% of initial values, they used albuterol at least 6 of the last 7 days, and they had asthma symptom scores of 2 (on a 0 to 5 scale) for at least 4 of the last 7 days.
STUDY DESIGN AND VALIDITY: This study was a double-blinded, randomized trial sponsored by the makers of fluticasone. Patients meeting initial inclusion criteria underwent an 8- to 14-day run-in period in which only short-acting beta-agonist use was allowed. Patients were then randomized to 1 of 2 treatment groups if they met the secondary inclusion criteria. Personal communication with the lead author confirmed that allocation assignment was concealed. Patients received either fluticasone 88 μg twice daily via metered dose inhaler (MDI) and montelukast placebo, or montelukast 10 mg daily with a placebo MDI. Patients kept daily records and had clinical evaluations at regular intervals for 24 weeks. Seventy-six percent of the patients completed the study.
OUTCOMES MEASURED: The primary outcome was percent change in FEV 1 . Other outcomes included peak flow rate, symptom-free days, daily albuterol use, asthma symptom scores, asthma quality-of-life scores, and patient-rated satisfaction with treatment. Safety was also assessed by reports of clinical adverse events and number of asthma exacerbations.
RESULTS: Using an intent-to-treat analysis, the fluticasone group had a significantly greater sustained change in FEV 1 (22% vs 14%; P < .001). Significant differences were noted after just 2 weeks of treatment. Significant differences favoring fluticasone were also found in all secondary outcomes including the patient-oriented outcomes of change in asthma symptom scores (–0.91 vs –0.57; P < .001), asthma quality-of-life scores (1.3 vs 1.0; P = .004), and patient-rated satisfaction with treatment (83% of fluticasone patients satisfied vs 66% of montelukast patients satisfied; P < .001). No differences were noted in overall incidence of adverse events between treatment groups, but significantly more fluticasone-treated patients reported hoarseness (9 vs 0; P = .002) and oral pharyngeal candidiasis (8 vs 0; P = .008). The incidence of asthma exacerbations was similar (19 fluticasone-treated patients vs 21 montelukast-treated patients).

ABSTRACT

BACKGROUND: Asthma management guidelines recommend patients with persistent asthma use asthma controller therapy in addition to as-needed short-acting beta-agonist therapy to improve symptom control, maintain pulmonary function, and decrease exacerbations. This study compared 2 asthma controllers, inhaled fluticasone and oral montelukast, with respect to clinical efficacy, patient preference, asthma-specific quality of life, and safety.
POPULATION STUDIED: The patients in this study were men and women aged 15 years and older with asthma recruited from multiple centers across the United States. Nonsmoking patients were included with a forced expiratory volume in 1 second (FEV 1 ) of 50% to 80% of predicted that reversed by at least 15% with bronchodilator use. Patients were then eligible for randomization if, after an 8- to 14-day run-in period, their FEV 1 remained within 15% of initial values, they used albuterol at least 6 of the last 7 days, and they had asthma symptom scores of 2 (on a 0 to 5 scale) for at least 4 of the last 7 days.
STUDY DESIGN AND VALIDITY: This study was a double-blinded, randomized trial sponsored by the makers of fluticasone. Patients meeting initial inclusion criteria underwent an 8- to 14-day run-in period in which only short-acting beta-agonist use was allowed. Patients were then randomized to 1 of 2 treatment groups if they met the secondary inclusion criteria. Personal communication with the lead author confirmed that allocation assignment was concealed. Patients received either fluticasone 88 μg twice daily via metered dose inhaler (MDI) and montelukast placebo, or montelukast 10 mg daily with a placebo MDI. Patients kept daily records and had clinical evaluations at regular intervals for 24 weeks. Seventy-six percent of the patients completed the study.
OUTCOMES MEASURED: The primary outcome was percent change in FEV 1 . Other outcomes included peak flow rate, symptom-free days, daily albuterol use, asthma symptom scores, asthma quality-of-life scores, and patient-rated satisfaction with treatment. Safety was also assessed by reports of clinical adverse events and number of asthma exacerbations.
RESULTS: Using an intent-to-treat analysis, the fluticasone group had a significantly greater sustained change in FEV 1 (22% vs 14%; P < .001). Significant differences were noted after just 2 weeks of treatment. Significant differences favoring fluticasone were also found in all secondary outcomes including the patient-oriented outcomes of change in asthma symptom scores (–0.91 vs –0.57; P < .001), asthma quality-of-life scores (1.3 vs 1.0; P = .004), and patient-rated satisfaction with treatment (83% of fluticasone patients satisfied vs 66% of montelukast patients satisfied; P < .001). No differences were noted in overall incidence of adverse events between treatment groups, but significantly more fluticasone-treated patients reported hoarseness (9 vs 0; P = .002) and oral pharyngeal candidiasis (8 vs 0; P = .008). The incidence of asthma exacerbations was similar (19 fluticasone-treated patients vs 21 montelukast-treated patients).

Evidence summary

Several systematic reviews help clarify theophylline’s role in asthma management. When compared with placebo in the management of acute exacerbations, theophylline confers no added benefit to beta-agonist therapy (with or without steroids) in improving pulmonary function or reducing hospitalization rates. Side effects occurred more often in the theophylline group: palpitations/arrhythmias (OR = 2.9; 95% CI: 1.5 to 5.7) and vomiting (OR = 4.2; 95% CI: 2.4 to 7.4).¹ For moderately severe asthma in patients already receiving inhaled corticosteroids (ICS), theophylline as maintenance therapy equaled long-acting beta-2-agonists in increasing FEV 1 and PEFR, but was less effective in controlling night time symptoms. Use of long-acting beta-agonists resulted in fewer side effects (RR = 0.38; 95%CI: 0.25-0.57).² When added to low-dose ICS for maintenance, theophylline was as effective as high-dose ICS alone in improving FEV 1 , decreasing day and night symptoms, and reducing the need for rescue medications and the incidence of attacks. This suggests theophylline has utility as a steroid sparing agent.³

Intravenous aminophylline does appear to be clinically beneficial for children with severe exacerbations, defined as an FEV 1 of 35%-40% of predicted value. Critically ill children receiving aminophylline in addition to usual care exhibited an improved FEV 1 at 24 hours (mean difference = 8.4%; 95% CI: 0.82 to 15.92) and reduced symptom scores at 6 hours.⁴ The largest RCT of aminophylline in children demonstrated a reduced intubation rate (NNT = 14 CI: 7.8-77).⁵ Children receiving aminophylline experienced more vomiting (RR = 3.69; 95%CI: 2.15-6.33). Treatment with aminophylline did not reduce length of hospital stay or the number of rescue nebulizers needed (Table).⁴

TABLE
Theophylline use in asthma

Recommendations from others

Three evidence-supported guidelines concur that theophylline has a limited role as maintenance therapy for moderate-to-severe persistent asthma when symptom control with ICS alone is not adequate. Much stronger evidence supports the use of long-acting beta-2-agonists or leukotriene modifiers in this setting.^6-8 The guidelines do not recommend using theophylline to treat acute asthma exacerbations; nor do they address using theophylline in children.

Read a Clinical Commentary by M. Lee Chambliss, MD, MSPH, at www.fpin.org.

Evidence summary

Several systematic reviews help clarify theophylline’s role in asthma management. When compared with placebo in the management of acute exacerbations, theophylline confers no added benefit to beta-agonist therapy (with or without steroids) in improving pulmonary function or reducing hospitalization rates. Side effects occurred more often in the theophylline group: palpitations/arrhythmias (OR = 2.9; 95% CI: 1.5 to 5.7) and vomiting (OR = 4.2; 95% CI: 2.4 to 7.4).¹ For moderately severe asthma in patients already receiving inhaled corticosteroids (ICS), theophylline as maintenance therapy equaled long-acting beta-2-agonists in increasing FEV 1 and PEFR, but was less effective in controlling night time symptoms. Use of long-acting beta-agonists resulted in fewer side effects (RR = 0.38; 95%CI: 0.25-0.57).² When added to low-dose ICS for maintenance, theophylline was as effective as high-dose ICS alone in improving FEV 1 , decreasing day and night symptoms, and reducing the need for rescue medications and the incidence of attacks. This suggests theophylline has utility as a steroid sparing agent.³

Intravenous aminophylline does appear to be clinically beneficial for children with severe exacerbations, defined as an FEV 1 of 35%-40% of predicted value. Critically ill children receiving aminophylline in addition to usual care exhibited an improved FEV 1 at 24 hours (mean difference = 8.4%; 95% CI: 0.82 to 15.92) and reduced symptom scores at 6 hours.⁴ The largest RCT of aminophylline in children demonstrated a reduced intubation rate (NNT = 14 CI: 7.8-77).⁵ Children receiving aminophylline experienced more vomiting (RR = 3.69; 95%CI: 2.15-6.33). Treatment with aminophylline did not reduce length of hospital stay or the number of rescue nebulizers needed (Table).⁴

TABLE
Theophylline use in asthma

Recommendations from others

Three evidence-supported guidelines concur that theophylline has a limited role as maintenance therapy for moderate-to-severe persistent asthma when symptom control with ICS alone is not adequate. Much stronger evidence supports the use of long-acting beta-2-agonists or leukotriene modifiers in this setting.^6-8 The guidelines do not recommend using theophylline to treat acute asthma exacerbations; nor do they address using theophylline in children.

Read a Clinical Commentary by M. Lee Chambliss, MD, MSPH, at www.fpin.org.

Evidence summary

Several systematic reviews help clarify theophylline’s role in asthma management. When compared with placebo in the management of acute exacerbations, theophylline confers no added benefit to beta-agonist therapy (with or without steroids) in improving pulmonary function or reducing hospitalization rates. Side effects occurred more often in the theophylline group: palpitations/arrhythmias (OR = 2.9; 95% CI: 1.5 to 5.7) and vomiting (OR = 4.2; 95% CI: 2.4 to 7.4).¹ For moderately severe asthma in patients already receiving inhaled corticosteroids (ICS), theophylline as maintenance therapy equaled long-acting beta-2-agonists in increasing FEV 1 and PEFR, but was less effective in controlling night time symptoms. Use of long-acting beta-agonists resulted in fewer side effects (RR = 0.38; 95%CI: 0.25-0.57).² When added to low-dose ICS for maintenance, theophylline was as effective as high-dose ICS alone in improving FEV 1 , decreasing day and night symptoms, and reducing the need for rescue medications and the incidence of attacks. This suggests theophylline has utility as a steroid sparing agent.³

Intravenous aminophylline does appear to be clinically beneficial for children with severe exacerbations, defined as an FEV 1 of 35%-40% of predicted value. Critically ill children receiving aminophylline in addition to usual care exhibited an improved FEV 1 at 24 hours (mean difference = 8.4%; 95% CI: 0.82 to 15.92) and reduced symptom scores at 6 hours.⁴ The largest RCT of aminophylline in children demonstrated a reduced intubation rate (NNT = 14 CI: 7.8-77).⁵ Children receiving aminophylline experienced more vomiting (RR = 3.69; 95%CI: 2.15-6.33). Treatment with aminophylline did not reduce length of hospital stay or the number of rescue nebulizers needed (Table).⁴

TABLE
Theophylline use in asthma

Recommendations from others

Three evidence-supported guidelines concur that theophylline has a limited role as maintenance therapy for moderate-to-severe persistent asthma when symptom control with ICS alone is not adequate. Much stronger evidence supports the use of long-acting beta-2-agonists or leukotriene modifiers in this setting.^6-8 The guidelines do not recommend using theophylline to treat acute asthma exacerbations; nor do they address using theophylline in children.

Read a Clinical Commentary by M. Lee Chambliss, MD, MSPH, at www.fpin.org.

ABSTRACT

BACKGROUND: Many individuals with asthma are allergic to house dust mites. The incidence and severity of asthma is increasing. More people are seeking complementary medical care, including homeopathy. Homeopathy attempts to mitigate disease by diluting the treatment without diluting the effect.

POPULATION STUDIED: The investigators recruited 1000 asthmatic outpatients from 38 general practices in Hampshire and Dorset, England. Of these, 327 tested positive for house dust mite allergy. Eighty-five patients were excluded for asthma that was either too mild or too well-controlled. Thus 242 subjects between 18 and 55 years old were randomized into the study. This group included both sexes; no note was made of race.

STUDY DESIGN AND VALIDITY: A double-blind, randomized control design was used. A French manufacturer of homeopathic products prepared the active agent by making 30 sequential 1:100 dilutions of a house dust mite allergen (this “ultramolecular” is a highly diluted solution of allergen molecules). After a 4-week period to assess baseline symptoms, subjects were randomized to receive either an oral homeopathic immunotherapy preparation or a similarly prepared placebo in 3 doses over 24 hours. They were then followed for 16 weeks with 3 clinic visits and every-other-week symptom diaries.

OUTCOMES MEASURED: Primary outcomes were change in lung function as measured by forced expiratory volume in 1 second (FEV₁) and quality of life as measured by proportion of symptom-free days in each 7-day diary period. Other outcomes included peak expiratory flow, scores for asthma visual analogue scale, and average mood scores.

RESULTS: This homeopathic therapy showed no significant improvement over placebo with regard to FEV₁ (0.136 L/sec active agent vs 0.414 L/sec placebo, 95% confidence interval [CI] =0.136–0.693) or mean improvement in quality of life (0.090 active agent vs 0.117 placebo, 95% CI = –.096 to .0150). Neither was there any significant difference in any of the secondary outcomes. These results were independent of the subjects’ belief in complementary medicine. Interestingly, at different times during the study improvement was noted in both the active therapy and placebo groups in FEV₁, quality of life, and mood.

ABSTRACT

BACKGROUND: Many individuals with asthma are allergic to house dust mites. The incidence and severity of asthma is increasing. More people are seeking complementary medical care, including homeopathy. Homeopathy attempts to mitigate disease by diluting the treatment without diluting the effect.

POPULATION STUDIED: The investigators recruited 1000 asthmatic outpatients from 38 general practices in Hampshire and Dorset, England. Of these, 327 tested positive for house dust mite allergy. Eighty-five patients were excluded for asthma that was either too mild or too well-controlled. Thus 242 subjects between 18 and 55 years old were randomized into the study. This group included both sexes; no note was made of race.

STUDY DESIGN AND VALIDITY: A double-blind, randomized control design was used. A French manufacturer of homeopathic products prepared the active agent by making 30 sequential 1:100 dilutions of a house dust mite allergen (this “ultramolecular” is a highly diluted solution of allergen molecules). After a 4-week period to assess baseline symptoms, subjects were randomized to receive either an oral homeopathic immunotherapy preparation or a similarly prepared placebo in 3 doses over 24 hours. They were then followed for 16 weeks with 3 clinic visits and every-other-week symptom diaries.

OUTCOMES MEASURED: Primary outcomes were change in lung function as measured by forced expiratory volume in 1 second (FEV₁) and quality of life as measured by proportion of symptom-free days in each 7-day diary period. Other outcomes included peak expiratory flow, scores for asthma visual analogue scale, and average mood scores.

RESULTS: This homeopathic therapy showed no significant improvement over placebo with regard to FEV₁ (0.136 L/sec active agent vs 0.414 L/sec placebo, 95% confidence interval [CI] =0.136–0.693) or mean improvement in quality of life (0.090 active agent vs 0.117 placebo, 95% CI = –.096 to .0150). Neither was there any significant difference in any of the secondary outcomes. These results were independent of the subjects’ belief in complementary medicine. Interestingly, at different times during the study improvement was noted in both the active therapy and placebo groups in FEV₁, quality of life, and mood.

ABSTRACT

BACKGROUND: Many individuals with asthma are allergic to house dust mites. The incidence and severity of asthma is increasing. More people are seeking complementary medical care, including homeopathy. Homeopathy attempts to mitigate disease by diluting the treatment without diluting the effect.

POPULATION STUDIED: The investigators recruited 1000 asthmatic outpatients from 38 general practices in Hampshire and Dorset, England. Of these, 327 tested positive for house dust mite allergy. Eighty-five patients were excluded for asthma that was either too mild or too well-controlled. Thus 242 subjects between 18 and 55 years old were randomized into the study. This group included both sexes; no note was made of race.

STUDY DESIGN AND VALIDITY: A double-blind, randomized control design was used. A French manufacturer of homeopathic products prepared the active agent by making 30 sequential 1:100 dilutions of a house dust mite allergen (this “ultramolecular” is a highly diluted solution of allergen molecules). After a 4-week period to assess baseline symptoms, subjects were randomized to receive either an oral homeopathic immunotherapy preparation or a similarly prepared placebo in 3 doses over 24 hours. They were then followed for 16 weeks with 3 clinic visits and every-other-week symptom diaries.

OUTCOMES MEASURED: Primary outcomes were change in lung function as measured by forced expiratory volume in 1 second (FEV₁) and quality of life as measured by proportion of symptom-free days in each 7-day diary period. Other outcomes included peak expiratory flow, scores for asthma visual analogue scale, and average mood scores.

RESULTS: This homeopathic therapy showed no significant improvement over placebo with regard to FEV₁ (0.136 L/sec active agent vs 0.414 L/sec placebo, 95% confidence interval [CI] =0.136–0.693) or mean improvement in quality of life (0.090 active agent vs 0.117 placebo, 95% CI = –.096 to .0150). Neither was there any significant difference in any of the secondary outcomes. These results were independent of the subjects’ belief in complementary medicine. Interestingly, at different times during the study improvement was noted in both the active therapy and placebo groups in FEV₁, quality of life, and mood.

ABSTRACT

BACKGROUND: Historically, nebulizers have been preferred over metered-dose inhalers (MDIs) for the treatment of asthma exacerbations, although numerous studies have shown their equivalence. A systematic review of 21 randomized trials supported the equivalence of an MDI with spacer and a nebulizer; the method of albuterol delivery did not affect hospital admission rates, length of stay in the emergency department, or measures of pulmonary function.¹ Advantages of MDIs may include lower costs, less excess drug exposure, and easier use for patients and physicians.

POPULATION STUDIED: The study population consisted of all patients older than 18 years who presented to an emergency department over a 2.5-year period with an asthma exacerbation (2342 visits, 1429 patients). Most patients were African American (75.4%). Most were women (58.6%), and the mean age was 35.5 ± 13.5 years.

STUDY DESIGN AND VALIDITY: The study was a large, prospective, unblinded, and nonrandomized trial consisting of 2 phases. For the first 12 months, physicians, using standard National Institues of Health guidelines, began treatment with a nebulizer (913 visits). Then for the next 18 months, physicians began treatment with albuterol delivered via MDI and spacer (1429 visits). The dose was 5 puffs, then 3 to 5 puffs every 20 minutes as needed. At the time of discharge from the emergency department during the MDI phase of the study, patients received a peak flow meter, an MDI and spacer, an inhaled corticosteroid, written materials, and counseling by emergency department nurses.

OUTCOMES MEASURED: The outcomes measured were PEFR, Sao ₂, heart and respiratory rates, total albuterol dose, and the more patient-oriented outcomes of rate of hospital admission, relapse rate, time in the emergency department, and costs.

RESULTS: In the MDI phase, post-albuterol PEFR was 11.0% higher (342 L/min vs 308 L/min; P = .001) and change in PEFR was 13.3% higher (127 L/min vs 112 L/min; P = .002). Change in Sao ₂ was significant (P = .043), and the total albuterol dose was significantly less in the MDI group (1125 μg vs 6700 μg; P = .001). However, these differences did not result in significantly lower hospital admission rates. Relapse rates were significantly lower at both 14 and 21 days in the MDI phase (6.6% and 10.7% vs 9.6% and 13.5%; P < .01 and P < .05). Patients treated with MDIs spent 6.5% less time in the emergency department (163.6 min vs 175.0 min; P = .007). The difference in visit charges was not significant.

ABSTRACT

BACKGROUND: Historically, nebulizers have been preferred over metered-dose inhalers (MDIs) for the treatment of asthma exacerbations, although numerous studies have shown their equivalence. A systematic review of 21 randomized trials supported the equivalence of an MDI with spacer and a nebulizer; the method of albuterol delivery did not affect hospital admission rates, length of stay in the emergency department, or measures of pulmonary function.¹ Advantages of MDIs may include lower costs, less excess drug exposure, and easier use for patients and physicians.

POPULATION STUDIED: The study population consisted of all patients older than 18 years who presented to an emergency department over a 2.5-year period with an asthma exacerbation (2342 visits, 1429 patients). Most patients were African American (75.4%). Most were women (58.6%), and the mean age was 35.5 ± 13.5 years.

STUDY DESIGN AND VALIDITY: The study was a large, prospective, unblinded, and nonrandomized trial consisting of 2 phases. For the first 12 months, physicians, using standard National Institues of Health guidelines, began treatment with a nebulizer (913 visits). Then for the next 18 months, physicians began treatment with albuterol delivered via MDI and spacer (1429 visits). The dose was 5 puffs, then 3 to 5 puffs every 20 minutes as needed. At the time of discharge from the emergency department during the MDI phase of the study, patients received a peak flow meter, an MDI and spacer, an inhaled corticosteroid, written materials, and counseling by emergency department nurses.

OUTCOMES MEASURED: The outcomes measured were PEFR, Sao ₂, heart and respiratory rates, total albuterol dose, and the more patient-oriented outcomes of rate of hospital admission, relapse rate, time in the emergency department, and costs.

RESULTS: In the MDI phase, post-albuterol PEFR was 11.0% higher (342 L/min vs 308 L/min; P = .001) and change in PEFR was 13.3% higher (127 L/min vs 112 L/min; P = .002). Change in Sao ₂ was significant (P = .043), and the total albuterol dose was significantly less in the MDI group (1125 μg vs 6700 μg; P = .001). However, these differences did not result in significantly lower hospital admission rates. Relapse rates were significantly lower at both 14 and 21 days in the MDI phase (6.6% and 10.7% vs 9.6% and 13.5%; P < .01 and P < .05). Patients treated with MDIs spent 6.5% less time in the emergency department (163.6 min vs 175.0 min; P = .007). The difference in visit charges was not significant.

ABSTRACT

BACKGROUND: Historically, nebulizers have been preferred over metered-dose inhalers (MDIs) for the treatment of asthma exacerbations, although numerous studies have shown their equivalence. A systematic review of 21 randomized trials supported the equivalence of an MDI with spacer and a nebulizer; the method of albuterol delivery did not affect hospital admission rates, length of stay in the emergency department, or measures of pulmonary function.¹ Advantages of MDIs may include lower costs, less excess drug exposure, and easier use for patients and physicians.

POPULATION STUDIED: The study population consisted of all patients older than 18 years who presented to an emergency department over a 2.5-year period with an asthma exacerbation (2342 visits, 1429 patients). Most patients were African American (75.4%). Most were women (58.6%), and the mean age was 35.5 ± 13.5 years.

STUDY DESIGN AND VALIDITY: The study was a large, prospective, unblinded, and nonrandomized trial consisting of 2 phases. For the first 12 months, physicians, using standard National Institues of Health guidelines, began treatment with a nebulizer (913 visits). Then for the next 18 months, physicians began treatment with albuterol delivered via MDI and spacer (1429 visits). The dose was 5 puffs, then 3 to 5 puffs every 20 minutes as needed. At the time of discharge from the emergency department during the MDI phase of the study, patients received a peak flow meter, an MDI and spacer, an inhaled corticosteroid, written materials, and counseling by emergency department nurses.

OUTCOMES MEASURED: The outcomes measured were PEFR, Sao ₂, heart and respiratory rates, total albuterol dose, and the more patient-oriented outcomes of rate of hospital admission, relapse rate, time in the emergency department, and costs.

RESULTS: In the MDI phase, post-albuterol PEFR was 11.0% higher (342 L/min vs 308 L/min; P = .001) and change in PEFR was 13.3% higher (127 L/min vs 112 L/min; P = .002). Change in Sao ₂ was significant (P = .043), and the total albuterol dose was significantly less in the MDI group (1125 μg vs 6700 μg; P = .001). However, these differences did not result in significantly lower hospital admission rates. Relapse rates were significantly lower at both 14 and 21 days in the MDI phase (6.6% and 10.7% vs 9.6% and 13.5%; P < .01 and P < .05). Patients treated with MDIs spent 6.5% less time in the emergency department (163.6 min vs 175.0 min; P = .007). The difference in visit charges was not significant.

ABSTRACT

BACKGROUND: Bolus intravenous (IV) albuterol (salbutamol) improved outcomes in pediatric patients with severe asthma exacerbations in 1 earlier small study. Previous studies demonstrated that the addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether combining the therapies results in earlier hospital discharge. This study compared these 2 approaches to determine their relative benefit in children with acute severe asthma.

POPULATION STUDIED: The researchers studied 55 children (aged 1–14 years) presenting with severe acute asthma to the emergency department of a ter-tiary children’s hospital in Sydney, Australia. Children were classified as having severe asthma if they had all 4 features of respiratory distress (wheezing, sternal retraction, accessory muscle use, and dyspnea) or had any of the absolute criteria (cyanosis, pulsus paradoxus, altered consciousness, or a silent chest auscultation). Baseline demographics and clinical characteristics were similar. Children who were excluded included those with life-threatening asthma, age younger than 12 months, presence of heart disease, family history of Wolff-Parkinson-White or past supraventricular tachycardia, other respiratory disease, or pneumonia, and those who had received inhaled ipratropium bromide that day.

STUDY DESIGN AND VALIDITY: This was a randomized, double-blind, double-dummy trial. The enrolling physician, treating physician, and assessor of outcome were all blinded. All children received 1 dose of nebulized albuterol 2.5 or 5 mg, then were assessed for asthma severity. Children meeting inclusion criteria received oxygen as needed, 1 mg/kg IV bolus methylprednisolone, and nebulized albuterol every 20 minutes for the first hour. The frequency of nebulized albuterol was then decreased based on clinical improvement. Patients were then randomized to receive IV albuterol (15 μg/kg); IV saline and inhaled ipratropium bromide (250 mg) every 20 minutes; or IV albuterol (15 μg/kg) and inhaled ipratropium bromide (250 μg) every 20 minutes. Asthma severity was assessed at 1 and 2 hours into the study using the clinical assessment scale and pulmonary index score. All 55 children completed the study.

OUTCOMES MEASURED: The primary outcomes for this study were mean recovery time (time from randomization to when patients no longer needed nebulized albuterol of a given frequency) and mean discharge time from the hospital. Secondary outcomes included clinical signs of moderate to severe asthma 2 hours after randomization and incidence of medication-related side effects.

RESULTS: Children treated with IV albuterol showed a significant benefit over those treated with inhaled ipratropium in recovery at 90, 120, and 180 minutes (P = .007, .01, and .004, respectively). Children in the IV albuterol group were ready for discharge 28.0 hours earlier than those in the ipratropium group (48.3 vs 76.3 hours; P = .005). The combination of IV albuterol and ipratropium showed a significant benefit over ipratropium alone in recovery time at 90 and 120 minutes (P = .02 and .008, respectively). However, no significant difference was evident between the combination and ipratropium alone in time to discharge (57.6 vs 76.3 hours, respectively; P = .2). The combination demonstrated no significant benefit over IV albuterol for any outcome. No significant adverse effects were documented in any of the patients, including tachycardia of more than 200 beats per minute for at least 5 minutes.

ABSTRACT

BACKGROUND: Bolus intravenous (IV) albuterol (salbutamol) improved outcomes in pediatric patients with severe asthma exacerbations in 1 earlier small study. Previous studies demonstrated that the addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether combining the therapies results in earlier hospital discharge. This study compared these 2 approaches to determine their relative benefit in children with acute severe asthma.

POPULATION STUDIED: The researchers studied 55 children (aged 1–14 years) presenting with severe acute asthma to the emergency department of a ter-tiary children’s hospital in Sydney, Australia. Children were classified as having severe asthma if they had all 4 features of respiratory distress (wheezing, sternal retraction, accessory muscle use, and dyspnea) or had any of the absolute criteria (cyanosis, pulsus paradoxus, altered consciousness, or a silent chest auscultation). Baseline demographics and clinical characteristics were similar. Children who were excluded included those with life-threatening asthma, age younger than 12 months, presence of heart disease, family history of Wolff-Parkinson-White or past supraventricular tachycardia, other respiratory disease, or pneumonia, and those who had received inhaled ipratropium bromide that day.

STUDY DESIGN AND VALIDITY: This was a randomized, double-blind, double-dummy trial. The enrolling physician, treating physician, and assessor of outcome were all blinded. All children received 1 dose of nebulized albuterol 2.5 or 5 mg, then were assessed for asthma severity. Children meeting inclusion criteria received oxygen as needed, 1 mg/kg IV bolus methylprednisolone, and nebulized albuterol every 20 minutes for the first hour. The frequency of nebulized albuterol was then decreased based on clinical improvement. Patients were then randomized to receive IV albuterol (15 μg/kg); IV saline and inhaled ipratropium bromide (250 mg) every 20 minutes; or IV albuterol (15 μg/kg) and inhaled ipratropium bromide (250 μg) every 20 minutes. Asthma severity was assessed at 1 and 2 hours into the study using the clinical assessment scale and pulmonary index score. All 55 children completed the study.

OUTCOMES MEASURED: The primary outcomes for this study were mean recovery time (time from randomization to when patients no longer needed nebulized albuterol of a given frequency) and mean discharge time from the hospital. Secondary outcomes included clinical signs of moderate to severe asthma 2 hours after randomization and incidence of medication-related side effects.

RESULTS: Children treated with IV albuterol showed a significant benefit over those treated with inhaled ipratropium in recovery at 90, 120, and 180 minutes (P = .007, .01, and .004, respectively). Children in the IV albuterol group were ready for discharge 28.0 hours earlier than those in the ipratropium group (48.3 vs 76.3 hours; P = .005). The combination of IV albuterol and ipratropium showed a significant benefit over ipratropium alone in recovery time at 90 and 120 minutes (P = .02 and .008, respectively). However, no significant difference was evident between the combination and ipratropium alone in time to discharge (57.6 vs 76.3 hours, respectively; P = .2). The combination demonstrated no significant benefit over IV albuterol for any outcome. No significant adverse effects were documented in any of the patients, including tachycardia of more than 200 beats per minute for at least 5 minutes.

ABSTRACT

BACKGROUND: Bolus intravenous (IV) albuterol (salbutamol) improved outcomes in pediatric patients with severe asthma exacerbations in 1 earlier small study. Previous studies demonstrated that the addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether combining the therapies results in earlier hospital discharge. This study compared these 2 approaches to determine their relative benefit in children with acute severe asthma.

POPULATION STUDIED: The researchers studied 55 children (aged 1–14 years) presenting with severe acute asthma to the emergency department of a ter-tiary children’s hospital in Sydney, Australia. Children were classified as having severe asthma if they had all 4 features of respiratory distress (wheezing, sternal retraction, accessory muscle use, and dyspnea) or had any of the absolute criteria (cyanosis, pulsus paradoxus, altered consciousness, or a silent chest auscultation). Baseline demographics and clinical characteristics were similar. Children who were excluded included those with life-threatening asthma, age younger than 12 months, presence of heart disease, family history of Wolff-Parkinson-White or past supraventricular tachycardia, other respiratory disease, or pneumonia, and those who had received inhaled ipratropium bromide that day.

STUDY DESIGN AND VALIDITY: This was a randomized, double-blind, double-dummy trial. The enrolling physician, treating physician, and assessor of outcome were all blinded. All children received 1 dose of nebulized albuterol 2.5 or 5 mg, then were assessed for asthma severity. Children meeting inclusion criteria received oxygen as needed, 1 mg/kg IV bolus methylprednisolone, and nebulized albuterol every 20 minutes for the first hour. The frequency of nebulized albuterol was then decreased based on clinical improvement. Patients were then randomized to receive IV albuterol (15 μg/kg); IV saline and inhaled ipratropium bromide (250 mg) every 20 minutes; or IV albuterol (15 μg/kg) and inhaled ipratropium bromide (250 μg) every 20 minutes. Asthma severity was assessed at 1 and 2 hours into the study using the clinical assessment scale and pulmonary index score. All 55 children completed the study.

OUTCOMES MEASURED: The primary outcomes for this study were mean recovery time (time from randomization to when patients no longer needed nebulized albuterol of a given frequency) and mean discharge time from the hospital. Secondary outcomes included clinical signs of moderate to severe asthma 2 hours after randomization and incidence of medication-related side effects.

RESULTS: Children treated with IV albuterol showed a significant benefit over those treated with inhaled ipratropium in recovery at 90, 120, and 180 minutes (P = .007, .01, and .004, respectively). Children in the IV albuterol group were ready for discharge 28.0 hours earlier than those in the ipratropium group (48.3 vs 76.3 hours; P = .005). The combination of IV albuterol and ipratropium showed a significant benefit over ipratropium alone in recovery time at 90 and 120 minutes (P = .02 and .008, respectively). However, no significant difference was evident between the combination and ipratropium alone in time to discharge (57.6 vs 76.3 hours, respectively; P = .2). The combination demonstrated no significant benefit over IV albuterol for any outcome. No significant adverse effects were documented in any of the patients, including tachycardia of more than 200 beats per minute for at least 5 minutes.

Evidence summary

Although several studies have shown the benefit of placing asthmatic and allergic children in highly sanitized hospital and sanitarium environments,¹ benefit has been extremely difficult to prove with measures used in the child’s home. Only reducing tobacco smoke exposure has been shown to be beneficial. In a randomized trial of predominantly poor minority subjects, fewer acute asthma medical visits were needed by children whose household members underwent behavioral education aimed at decreasing smoke exposure.²

Other methods of modifying the environment have not proved beneficial. Although a group of researchers found that home visits by care providers may decrease acute medical visits, specific allergy avoidance steps did not make a difference.³ Two of these authors also reported that the use of chemicals for house dust mite control and the use of synthetic pillows in lieu of feather pillows may actually exacerbate asthma.⁴ A Cochrane review was inconclusive on the risks or benefits of feather bedding.⁵ Benefit from removing cats is difficult to prove because of the ubiquitous nature of cat antigen and the difficulty in eradicating it from the home. Using air filters and reducing indoor humidity have likewise failed to show meaningful improvement in peak flow, medication use, or symptom scores.

The effectiveness of physical methods to reduce house dust mites is unclear. The Cochrane Review of 15 trials noted a small, statistically significant improvement in asthma symptom scores, but the results were not clinically important enough to recommend such measures.⁶ The potential harm of chemical measures was reiterated in this review.

TABLE
Environmental modifications for children with asthma

Recommendations from others

The National Heart, Lung, and Blood Institute continues to recommend physical barriers to reduce house dust mite antigen based on 4 small trials in which the major benefit was decreased bronchial hyperresponsiveness.⁷ Larger trials, now under way, may help resolve the issue.

Clinical Commentary by Nicholas J. Solomos, MD, at http://www.fpin.org.

Evidence summary

Although several studies have shown the benefit of placing asthmatic and allergic children in highly sanitized hospital and sanitarium environments,¹ benefit has been extremely difficult to prove with measures used in the child’s home. Only reducing tobacco smoke exposure has been shown to be beneficial. In a randomized trial of predominantly poor minority subjects, fewer acute asthma medical visits were needed by children whose household members underwent behavioral education aimed at decreasing smoke exposure.²

Other methods of modifying the environment have not proved beneficial. Although a group of researchers found that home visits by care providers may decrease acute medical visits, specific allergy avoidance steps did not make a difference.³ Two of these authors also reported that the use of chemicals for house dust mite control and the use of synthetic pillows in lieu of feather pillows may actually exacerbate asthma.⁴ A Cochrane review was inconclusive on the risks or benefits of feather bedding.⁵ Benefit from removing cats is difficult to prove because of the ubiquitous nature of cat antigen and the difficulty in eradicating it from the home. Using air filters and reducing indoor humidity have likewise failed to show meaningful improvement in peak flow, medication use, or symptom scores.

The effectiveness of physical methods to reduce house dust mites is unclear. The Cochrane Review of 15 trials noted a small, statistically significant improvement in asthma symptom scores, but the results were not clinically important enough to recommend such measures.⁶ The potential harm of chemical measures was reiterated in this review.

TABLE
Environmental modifications for children with asthma

Recommendations from others

The National Heart, Lung, and Blood Institute continues to recommend physical barriers to reduce house dust mite antigen based on 4 small trials in which the major benefit was decreased bronchial hyperresponsiveness.⁷ Larger trials, now under way, may help resolve the issue.

Clinical Commentary by Nicholas J. Solomos, MD, at http://www.fpin.org.

Evidence summary

Although several studies have shown the benefit of placing asthmatic and allergic children in highly sanitized hospital and sanitarium environments,¹ benefit has been extremely difficult to prove with measures used in the child’s home. Only reducing tobacco smoke exposure has been shown to be beneficial. In a randomized trial of predominantly poor minority subjects, fewer acute asthma medical visits were needed by children whose household members underwent behavioral education aimed at decreasing smoke exposure.²

Other methods of modifying the environment have not proved beneficial. Although a group of researchers found that home visits by care providers may decrease acute medical visits, specific allergy avoidance steps did not make a difference.³ Two of these authors also reported that the use of chemicals for house dust mite control and the use of synthetic pillows in lieu of feather pillows may actually exacerbate asthma.⁴ A Cochrane review was inconclusive on the risks or benefits of feather bedding.⁵ Benefit from removing cats is difficult to prove because of the ubiquitous nature of cat antigen and the difficulty in eradicating it from the home. Using air filters and reducing indoor humidity have likewise failed to show meaningful improvement in peak flow, medication use, or symptom scores.

The effectiveness of physical methods to reduce house dust mites is unclear. The Cochrane Review of 15 trials noted a small, statistically significant improvement in asthma symptom scores, but the results were not clinically important enough to recommend such measures.⁶ The potential harm of chemical measures was reiterated in this review.

TABLE
Environmental modifications for children with asthma

Recommendations from others

The National Heart, Lung, and Blood Institute continues to recommend physical barriers to reduce house dust mite antigen based on 4 small trials in which the major benefit was decreased bronchial hyperresponsiveness.⁷ Larger trials, now under way, may help resolve the issue.

Clinical Commentary by Nicholas J. Solomos, MD, at http://www.fpin.org.

ABSTRACT

BACKGROUND: Adding 2 to 3 doses of ipratropium bromide (Atrovent) to conventional therapy with inhaled β-agonists and systemic corticosteroids improves lung function and decreases hospital admissions when given in the emergency department (ED). This study evaluated whether ipratropium bromide administration improves outcomes in children who require subsequent hospitalization.

POPULATION STUDIED: The authors enrolled 80 children aged 1 to 18 years with a history of asthma admitted to the pediatric inpatient unit of a tertiary-care urban hospital. Children had to have moderate to severe symptoms upon admission, defined as requiring inhaled β₂-agonists at least every 2 hours, having a forced expiratory volume in 1 second (FEV₁) of 25% to 80% of predicted, or having a clinical asthma score of 3 to 9 out of a possible 10. The clinical asthma score is a total of 5 items—respiratory rate, wheezing, inspiratory–expiratory ratio, retracting, and observed dyspnea—scored on a 3-point scale. Excluded patients had coexisting cardiac, neurologic, immunosuppressive, or other chronic pulmonary disease, hypersensitivity to the study drugs, or known ocular abnormalities. Children were excluded if their asthma score was 10, if they needed airway intervention, or if more than 12 hours had elapsed between the first nebulizer treatment and admission.

STUDY DESIGN AND VALIDITY: This was a double-blind randomized controlled trial. Study patients received frequent nebulized albuterol at 0.15 mg/kg as well as either IV hydrocortisone at 4 to 6 mg/kg every 6 hours or oral prednisone 1 mg/kg once daily. Attending physicians determined nebulizer treatment frequency, ranging from 30 minutes to 4 hours. Subjects were randomized to receive either ipratropium bromide or normal saline, matched to the albuterol dosing interval. Participants were stratified by age (less than 5 years vs 5 years or more) and by the number of ipratropium bromide doses they received in the ED (3 or less vs more than 3). Investigators used an intention-to-treat analysis and allocation was concealed.

OUTCOMES MEASURED: The primary outcome was the clinical asthma score, measured at baseline and every 6 hours until discharge. The clinical score is reproducible, valid, and predictive. Secondary outcomes included oxygen saturation, FEV₁, length of stay, time to a 4-hour albuterol dosing interval, and readmission to the hospital or ED within 72 hours of discharge.

RESULTS: Of the 212 patients assessed for the trial, only 99 were eligible. Of these, 84 parents consented to enroll their children (4 children were later determined not to meet inclusion criteria and were excluded). The ipratropium and placebo groups were essentially the same. There was no difference in the asthma score between treatment and control groups in 3 of the 4 subgroups. In one subgroup—those who had fewer than 3 doses of ipratropium bromide in the ED—ipratropium provided a slight benefit. The difference in change in scores was 0.5 on the clinical asthma score, a statistically but not clinically important change. There were no differences in the secondary outcomes. The average heart rate was 6 to 10 beats per minute greater in the ipratropium group. The authors noted no transient anisocoria, a potential adverse effect of ipratropium bromide in children.

ABSTRACT

BACKGROUND: Adding 2 to 3 doses of ipratropium bromide (Atrovent) to conventional therapy with inhaled β-agonists and systemic corticosteroids improves lung function and decreases hospital admissions when given in the emergency department (ED). This study evaluated whether ipratropium bromide administration improves outcomes in children who require subsequent hospitalization.

POPULATION STUDIED: The authors enrolled 80 children aged 1 to 18 years with a history of asthma admitted to the pediatric inpatient unit of a tertiary-care urban hospital. Children had to have moderate to severe symptoms upon admission, defined as requiring inhaled β₂-agonists at least every 2 hours, having a forced expiratory volume in 1 second (FEV₁) of 25% to 80% of predicted, or having a clinical asthma score of 3 to 9 out of a possible 10. The clinical asthma score is a total of 5 items—respiratory rate, wheezing, inspiratory–expiratory ratio, retracting, and observed dyspnea—scored on a 3-point scale. Excluded patients had coexisting cardiac, neurologic, immunosuppressive, or other chronic pulmonary disease, hypersensitivity to the study drugs, or known ocular abnormalities. Children were excluded if their asthma score was 10, if they needed airway intervention, or if more than 12 hours had elapsed between the first nebulizer treatment and admission.

STUDY DESIGN AND VALIDITY: This was a double-blind randomized controlled trial. Study patients received frequent nebulized albuterol at 0.15 mg/kg as well as either IV hydrocortisone at 4 to 6 mg/kg every 6 hours or oral prednisone 1 mg/kg once daily. Attending physicians determined nebulizer treatment frequency, ranging from 30 minutes to 4 hours. Subjects were randomized to receive either ipratropium bromide or normal saline, matched to the albuterol dosing interval. Participants were stratified by age (less than 5 years vs 5 years or more) and by the number of ipratropium bromide doses they received in the ED (3 or less vs more than 3). Investigators used an intention-to-treat analysis and allocation was concealed.

OUTCOMES MEASURED: The primary outcome was the clinical asthma score, measured at baseline and every 6 hours until discharge. The clinical score is reproducible, valid, and predictive. Secondary outcomes included oxygen saturation, FEV₁, length of stay, time to a 4-hour albuterol dosing interval, and readmission to the hospital or ED within 72 hours of discharge.

RESULTS: Of the 212 patients assessed for the trial, only 99 were eligible. Of these, 84 parents consented to enroll their children (4 children were later determined not to meet inclusion criteria and were excluded). The ipratropium and placebo groups were essentially the same. There was no difference in the asthma score between treatment and control groups in 3 of the 4 subgroups. In one subgroup—those who had fewer than 3 doses of ipratropium bromide in the ED—ipratropium provided a slight benefit. The difference in change in scores was 0.5 on the clinical asthma score, a statistically but not clinically important change. There were no differences in the secondary outcomes. The average heart rate was 6 to 10 beats per minute greater in the ipratropium group. The authors noted no transient anisocoria, a potential adverse effect of ipratropium bromide in children.

ABSTRACT

BACKGROUND: Adding 2 to 3 doses of ipratropium bromide (Atrovent) to conventional therapy with inhaled β-agonists and systemic corticosteroids improves lung function and decreases hospital admissions when given in the emergency department (ED). This study evaluated whether ipratropium bromide administration improves outcomes in children who require subsequent hospitalization.

POPULATION STUDIED: The authors enrolled 80 children aged 1 to 18 years with a history of asthma admitted to the pediatric inpatient unit of a tertiary-care urban hospital. Children had to have moderate to severe symptoms upon admission, defined as requiring inhaled β₂-agonists at least every 2 hours, having a forced expiratory volume in 1 second (FEV₁) of 25% to 80% of predicted, or having a clinical asthma score of 3 to 9 out of a possible 10. The clinical asthma score is a total of 5 items—respiratory rate, wheezing, inspiratory–expiratory ratio, retracting, and observed dyspnea—scored on a 3-point scale. Excluded patients had coexisting cardiac, neurologic, immunosuppressive, or other chronic pulmonary disease, hypersensitivity to the study drugs, or known ocular abnormalities. Children were excluded if their asthma score was 10, if they needed airway intervention, or if more than 12 hours had elapsed between the first nebulizer treatment and admission.

STUDY DESIGN AND VALIDITY: This was a double-blind randomized controlled trial. Study patients received frequent nebulized albuterol at 0.15 mg/kg as well as either IV hydrocortisone at 4 to 6 mg/kg every 6 hours or oral prednisone 1 mg/kg once daily. Attending physicians determined nebulizer treatment frequency, ranging from 30 minutes to 4 hours. Subjects were randomized to receive either ipratropium bromide or normal saline, matched to the albuterol dosing interval. Participants were stratified by age (less than 5 years vs 5 years or more) and by the number of ipratropium bromide doses they received in the ED (3 or less vs more than 3). Investigators used an intention-to-treat analysis and allocation was concealed.

OUTCOMES MEASURED: The primary outcome was the clinical asthma score, measured at baseline and every 6 hours until discharge. The clinical score is reproducible, valid, and predictive. Secondary outcomes included oxygen saturation, FEV₁, length of stay, time to a 4-hour albuterol dosing interval, and readmission to the hospital or ED within 72 hours of discharge.

RESULTS: Of the 212 patients assessed for the trial, only 99 were eligible. Of these, 84 parents consented to enroll their children (4 children were later determined not to meet inclusion criteria and were excluded). The ipratropium and placebo groups were essentially the same. There was no difference in the asthma score between treatment and control groups in 3 of the 4 subgroups. In one subgroup—those who had fewer than 3 doses of ipratropium bromide in the ED—ipratropium provided a slight benefit. The difference in change in scores was 0.5 on the clinical asthma score, a statistically but not clinically important change. There were no differences in the secondary outcomes. The average heart rate was 6 to 10 beats per minute greater in the ipratropium group. The authors noted no transient anisocoria, a potential adverse effect of ipratropium bromide in children.

Evidence summary

While many sources state that extraesophageal symptoms (eg, cough, chest pain, asthma) are reported by patients with GERD, only one study reported the frequency of associated symptoms.¹ This population-based survey showed that symptoms of reflux and acid regurgitation are experienced by almost 60% of the population each year. The prevalence of frequent heartburn and acid reflux was approximately 20%. Bronchitis, defined as cough that occurs as often as 4 to 6 times per day on 4 or more days per week, was reported by more than 20% of those with frequent typical GERD symptoms (occurring at least weekly) and by 15% of those with infrequent GERD symptoms. Interestingly, bronchitis was reported by almost 11% of those without GERD. This study showed the association of cough with GERD but did not address whether the cough was the initial presenting complaint.

In as many as 40% of patients with cough, GERD is the underlying cause.^2-7 Chronic cough may be triggered by more than one condition (eg, GERD, postnasal drip, or asthma) in 18% to 93% of patients.⁸ Among patients with cough caused by GERD, 50% to 75% do not have classic symptoms of reflux or regurgitation.⁹ Finally, cough may initiate GERD and start a cough–reflux cycle.⁹ These studies were conducted in pulmonary clinics. Patients with cough whose underlying GERD was easily diagnosed and treated by their primary physician were probably not referred for evaluation in a pulmonary clinic.

Recommendations from others

The American College of Chest Physicians issued a consensus statement in 1999 regarding the management of cough.¹⁰ According to the statement, GERD should be strongly suspected in coughing patients with upper GI symptoms or in those without GI symptoms who have normal chest radiographs, do not smoke, and do not take angiotensin-converting enzyme inhibitors. The statement reports that asthma, postnasal drip syndrome (PNDS), and GERD are the causes of cough in nearly 100% of these patients. The recommendation for evaluation of GERD is a 24-hour pH monitor or an empiric trial of antireflux medication after ruling out asthma and PNDS.

Evidence summary

While many sources state that extraesophageal symptoms (eg, cough, chest pain, asthma) are reported by patients with GERD, only one study reported the frequency of associated symptoms.¹ This population-based survey showed that symptoms of reflux and acid regurgitation are experienced by almost 60% of the population each year. The prevalence of frequent heartburn and acid reflux was approximately 20%. Bronchitis, defined as cough that occurs as often as 4 to 6 times per day on 4 or more days per week, was reported by more than 20% of those with frequent typical GERD symptoms (occurring at least weekly) and by 15% of those with infrequent GERD symptoms. Interestingly, bronchitis was reported by almost 11% of those without GERD. This study showed the association of cough with GERD but did not address whether the cough was the initial presenting complaint.

In as many as 40% of patients with cough, GERD is the underlying cause.^2-7 Chronic cough may be triggered by more than one condition (eg, GERD, postnasal drip, or asthma) in 18% to 93% of patients.⁸ Among patients with cough caused by GERD, 50% to 75% do not have classic symptoms of reflux or regurgitation.⁹ Finally, cough may initiate GERD and start a cough–reflux cycle.⁹ These studies were conducted in pulmonary clinics. Patients with cough whose underlying GERD was easily diagnosed and treated by their primary physician were probably not referred for evaluation in a pulmonary clinic.

Recommendations from others

The American College of Chest Physicians issued a consensus statement in 1999 regarding the management of cough.¹⁰ According to the statement, GERD should be strongly suspected in coughing patients with upper GI symptoms or in those without GI symptoms who have normal chest radiographs, do not smoke, and do not take angiotensin-converting enzyme inhibitors. The statement reports that asthma, postnasal drip syndrome (PNDS), and GERD are the causes of cough in nearly 100% of these patients. The recommendation for evaluation of GERD is a 24-hour pH monitor or an empiric trial of antireflux medication after ruling out asthma and PNDS.

Evidence summary

While many sources state that extraesophageal symptoms (eg, cough, chest pain, asthma) are reported by patients with GERD, only one study reported the frequency of associated symptoms.¹ This population-based survey showed that symptoms of reflux and acid regurgitation are experienced by almost 60% of the population each year. The prevalence of frequent heartburn and acid reflux was approximately 20%. Bronchitis, defined as cough that occurs as often as 4 to 6 times per day on 4 or more days per week, was reported by more than 20% of those with frequent typical GERD symptoms (occurring at least weekly) and by 15% of those with infrequent GERD symptoms. Interestingly, bronchitis was reported by almost 11% of those without GERD. This study showed the association of cough with GERD but did not address whether the cough was the initial presenting complaint.

In as many as 40% of patients with cough, GERD is the underlying cause.^2-7 Chronic cough may be triggered by more than one condition (eg, GERD, postnasal drip, or asthma) in 18% to 93% of patients.⁸ Among patients with cough caused by GERD, 50% to 75% do not have classic symptoms of reflux or regurgitation.⁹ Finally, cough may initiate GERD and start a cough–reflux cycle.⁹ These studies were conducted in pulmonary clinics. Patients with cough whose underlying GERD was easily diagnosed and treated by their primary physician were probably not referred for evaluation in a pulmonary clinic.

Recommendations from others

The American College of Chest Physicians issued a consensus statement in 1999 regarding the management of cough.¹⁰ According to the statement, GERD should be strongly suspected in coughing patients with upper GI symptoms or in those without GI symptoms who have normal chest radiographs, do not smoke, and do not take angiotensin-converting enzyme inhibitors. The statement reports that asthma, postnasal drip syndrome (PNDS), and GERD are the causes of cough in nearly 100% of these patients. The recommendation for evaluation of GERD is a 24-hour pH monitor or an empiric trial of antireflux medication after ruling out asthma and PNDS.

BACKGROUND: Dexamethasone, a long-acting corticosteroid successfully used in acute treatment of croup, may prevent more relapses than prednisone in asthmatic children.

POPULATION STUDIED: The authors studied known asthmatic persons (defined by 2 or more episodes of wheezing treated with b-agonists with or without steroids) aged 2 to 18 years presenting to a children’s health hospital emergency department (ED) with an acute asthma exacerbation requiring more than 1 albuterol nebulizer treatment. Nursing staff assessed asthma severity based on either peak expired flow rates or a validated asthma severity scoring system. Children were excluded for recent oral corticosteroid treatment, history of intubation, recent varicella exposure, stridor, possible foreign body, and certain chronic diseases. During an 11-month period, 628 subjects enrolled, of whom 533 (85%) completed the study. Two thirds were men, 84% were black, and the average age was between 6 and 7 years. Fifty-six percent of the children were classified as moderate asthma severity at presentation; the remainder was evenly distributed between mild and severe.

STUDY DESIGN AND VALIDITY: This controlled trial assigned children to receive oral prednisone (2 mg/kg, maximum 60 mg, n= 261) on odd days and dexamethasone (0.6 mg/kg, maximum 16 mg, n=272) on even days. The first dose was given in the ED; the prednisone group was sent home with a prescription for 4 daily doses, the dexamethasone group was given a prepackaged dose for the following day. Children who vomited 2 doses of steroid or were directly admitted to the hospital from the ED were dropped from the study.This was a quasirandomized study, in that children were placed on one drug on even days and the other steroid on odd days. As a result, the allocation to the specific treatment groups was not concealed. Although patient severity is unlikely to have varied systematically on even and odd days, a large potential exists for a bias to be introduced into this study. Nurses who believed one treatment was superior to another could have systematically altered enrollment of children into the study based on the treatment of that day. These 2 issues—lack of randomization and concealed allocation—could invalidate the results of the study. The majority of subjects were black. Asthma prevalence, morbidity, and mortality are higher among black children, especially those in urban settings.¹ There is also some evidence of physiologic predisposition in this population, namely, higher serum immunoglobulin E levels and increased airway responsiveness.² However, no literature suggests that there is a difference in asthma treatment response between black children and children of other races or ethnicities.

OUTCOMES MEASURED: The primary outcome was rate of relapse within 10 days of discharge from the ED. Secondary outcomes were rate of hospitalization, frequency of vomiting, medication compliance, persistence of symptoms, and work or school days missed.

RESULTS: By evaluating the children who completed the study, the authors determined that the relapse rates were similar between the 2 groups, 7.4% in the dexamethasone group and 6.9% in the prednisone group (P = NS). Intention-to-treat analysis also found no difference between treatments. The number of admissions after relapse and the prevalence of persistent symptoms was also similar between the 2 groups. More children in the prednisone group missed 2 or more school days (P =.05), and more parents in this group reported not giving the medication at home (P =.004).

BACKGROUND: Dexamethasone, a long-acting corticosteroid successfully used in acute treatment of croup, may prevent more relapses than prednisone in asthmatic children.

POPULATION STUDIED: The authors studied known asthmatic persons (defined by 2 or more episodes of wheezing treated with b-agonists with or without steroids) aged 2 to 18 years presenting to a children’s health hospital emergency department (ED) with an acute asthma exacerbation requiring more than 1 albuterol nebulizer treatment. Nursing staff assessed asthma severity based on either peak expired flow rates or a validated asthma severity scoring system. Children were excluded for recent oral corticosteroid treatment, history of intubation, recent varicella exposure, stridor, possible foreign body, and certain chronic diseases. During an 11-month period, 628 subjects enrolled, of whom 533 (85%) completed the study. Two thirds were men, 84% were black, and the average age was between 6 and 7 years. Fifty-six percent of the children were classified as moderate asthma severity at presentation; the remainder was evenly distributed between mild and severe.

STUDY DESIGN AND VALIDITY: This controlled trial assigned children to receive oral prednisone (2 mg/kg, maximum 60 mg, n= 261) on odd days and dexamethasone (0.6 mg/kg, maximum 16 mg, n=272) on even days. The first dose was given in the ED; the prednisone group was sent home with a prescription for 4 daily doses, the dexamethasone group was given a prepackaged dose for the following day. Children who vomited 2 doses of steroid or were directly admitted to the hospital from the ED were dropped from the study.This was a quasirandomized study, in that children were placed on one drug on even days and the other steroid on odd days. As a result, the allocation to the specific treatment groups was not concealed. Although patient severity is unlikely to have varied systematically on even and odd days, a large potential exists for a bias to be introduced into this study. Nurses who believed one treatment was superior to another could have systematically altered enrollment of children into the study based on the treatment of that day. These 2 issues—lack of randomization and concealed allocation—could invalidate the results of the study. The majority of subjects were black. Asthma prevalence, morbidity, and mortality are higher among black children, especially those in urban settings.¹ There is also some evidence of physiologic predisposition in this population, namely, higher serum immunoglobulin E levels and increased airway responsiveness.² However, no literature suggests that there is a difference in asthma treatment response between black children and children of other races or ethnicities.

OUTCOMES MEASURED: The primary outcome was rate of relapse within 10 days of discharge from the ED. Secondary outcomes were rate of hospitalization, frequency of vomiting, medication compliance, persistence of symptoms, and work or school days missed.

RESULTS: By evaluating the children who completed the study, the authors determined that the relapse rates were similar between the 2 groups, 7.4% in the dexamethasone group and 6.9% in the prednisone group (P = NS). Intention-to-treat analysis also found no difference between treatments. The number of admissions after relapse and the prevalence of persistent symptoms was also similar between the 2 groups. More children in the prednisone group missed 2 or more school days (P =.05), and more parents in this group reported not giving the medication at home (P =.004).

BACKGROUND: Dexamethasone, a long-acting corticosteroid successfully used in acute treatment of croup, may prevent more relapses than prednisone in asthmatic children.

POPULATION STUDIED: The authors studied known asthmatic persons (defined by 2 or more episodes of wheezing treated with b-agonists with or without steroids) aged 2 to 18 years presenting to a children’s health hospital emergency department (ED) with an acute asthma exacerbation requiring more than 1 albuterol nebulizer treatment. Nursing staff assessed asthma severity based on either peak expired flow rates or a validated asthma severity scoring system. Children were excluded for recent oral corticosteroid treatment, history of intubation, recent varicella exposure, stridor, possible foreign body, and certain chronic diseases. During an 11-month period, 628 subjects enrolled, of whom 533 (85%) completed the study. Two thirds were men, 84% were black, and the average age was between 6 and 7 years. Fifty-six percent of the children were classified as moderate asthma severity at presentation; the remainder was evenly distributed between mild and severe.

STUDY DESIGN AND VALIDITY: This controlled trial assigned children to receive oral prednisone (2 mg/kg, maximum 60 mg, n= 261) on odd days and dexamethasone (0.6 mg/kg, maximum 16 mg, n=272) on even days. The first dose was given in the ED; the prednisone group was sent home with a prescription for 4 daily doses, the dexamethasone group was given a prepackaged dose for the following day. Children who vomited 2 doses of steroid or were directly admitted to the hospital from the ED were dropped from the study.This was a quasirandomized study, in that children were placed on one drug on even days and the other steroid on odd days. As a result, the allocation to the specific treatment groups was not concealed. Although patient severity is unlikely to have varied systematically on even and odd days, a large potential exists for a bias to be introduced into this study. Nurses who believed one treatment was superior to another could have systematically altered enrollment of children into the study based on the treatment of that day. These 2 issues—lack of randomization and concealed allocation—could invalidate the results of the study. The majority of subjects were black. Asthma prevalence, morbidity, and mortality are higher among black children, especially those in urban settings.¹ There is also some evidence of physiologic predisposition in this population, namely, higher serum immunoglobulin E levels and increased airway responsiveness.² However, no literature suggests that there is a difference in asthma treatment response between black children and children of other races or ethnicities.

OUTCOMES MEASURED: The primary outcome was rate of relapse within 10 days of discharge from the ED. Secondary outcomes were rate of hospitalization, frequency of vomiting, medication compliance, persistence of symptoms, and work or school days missed.

RESULTS: By evaluating the children who completed the study, the authors determined that the relapse rates were similar between the 2 groups, 7.4% in the dexamethasone group and 6.9% in the prednisone group (P = NS). Intention-to-treat analysis also found no difference between treatments. The number of admissions after relapse and the prevalence of persistent symptoms was also similar between the 2 groups. More children in the prednisone group missed 2 or more school days (P =.05), and more parents in this group reported not giving the medication at home (P =.004).