Vol. 12 •Issue 6 • Page 12
Allergy & Asthma
Study Shines Light on Nocturnal Symptoms of Asthma
Nocturnal awakenings are a warning sign that asthma may be exacerbating. Our research of nocturnal asthma in 1,041 patients with mild to moderate asthma enrolled in the Childhood Asthma Management Program (CAMP) was the first thorough study of the problem in children.1
Children in CAMP had a history of mild to moderate asthma during at least six months prior to entering into the study. Forty percent of the children had been treated with low doses of controller medicines before enrollment and were able to stop the medications without exacerbation of their asthma.
None had histories of severe disease, such as more than one hospitalization in the year prior to entering, six or more courses of oral steroids, and history of respiratory failure. We specifically excluded patients using medicines for esophageal reflux.
Patients entered a 28-day screening interval to obtain baseline data on asthma symptoms, variability in peak flows morning to night, and records of awakening for asthma symptoms when taking only bronchodilators on an as-needed basis. As a safeguard against enrolling a child with severe asthma, there was a limit of 1.5 nights per week with awakening due to asthma symptoms during this 28-day observation period.
PREVALENCE OF AWAKENINGS
Nocturnal asthma was remarkably prevalent in the CAMP children studied. Thirty-four percent experienced one or more nighttime awakenings in the 28 days of observation. Most children had only one or two awakenings in this month (13 percent and 7 percent, respectively); 2 percent had six awakenings.
Most of the awakenings were isolated, with 62 percent occurring as single awakenings. But 23 percent occurred as consecutive awakenings, 9 percent as three consecutive awakenings, and 6 percent as four or five consecutive awakenings. It’s surprising that some of the CAMP patients had relatively large numbers of consecutive awakenings without going on to have an exacerbation requiring oral steroids.
The risk of night awakenings in the CAMP patients was much greater in patients who had more atopy, as indicated by higher total eosinophil counts in peripheral blood, higher total serum IgE levels, and more positive skin tests, as well as those having more severe asthma overall.
A greater risk of awakening also was associated with increases in reactivity to bronchodilator on pulmonary function testing, greater airway responsiveness to methacholine, greater peak flow variability, and more use of albuterol during the observation period.
Clinical indicators suggestive of unstable asthma were associated with nighttime awakenings: Evening peak flow less than 80 percent personal best the day before, symptom code increase from two days before to the day before awakening, and any albuterol use for symptoms the day before awakening all were associated with increased risk of a night awakening compared with the absence of the indicator (all p<0.0001).
The strongest risk factor for night awakening was prior night awakening. Night awakening one and two days before increased the risk nearly 14-fold, night awakening one day before increased risk 11-fold, and night awakening two days before increased risk sixfold.
Clinical indicators suggestive of stable asthma were associated with decreased risk of awakening. When evening peak flow was at least 80 percent of personal best, risk of a night awakening was only 65 percent of the risk of awakening after a day with evening peak flow of less than 80 percent of personal best (p<0.0001). Risk of night awakening after a day with evening peak flow of at least 80 percent of personal best, no use of albuterol for symptoms, and symptoms code of 0 for the day was 41 percent of the risk of awakening after a day with at least one of these indicators of unstable asthma (p<0.0001).
In contrast to the generalizations that can be made about risk factors for awakenings, predicting individual awakenings in a child was much more difficult. Data on symptoms, albuterol use and peak flows were examined in three-day intervals before awakenings compared to a time of stability four days to six days before awakenings.
While there were increases in symptoms and use of albuterol in the three days preceding an awakening, the changes were minimal and probably not clinically useful. Interestingly, there were no changes in peak flows in the three days before individual awakenings compared to other days that could have alerted parents to the possibility that an awakening would occur.
We examined the possibility that awakenings were an indicator of increased instability in the clinical course. Data for the three days after an episode compared to the three days before indicated more asthma after an awakening than before it occurred. As with the data used to examine predictors of awakening, data three days after an episode were different for overall symptom code and puffs of albuterol but not peak flow. It wasn’t until there were two or more consecutive nights that the peak flow decreased.
Because we were interested in the possibility that parents might be able to determine the likelihood of a second consecutive awakening occurring, we focused on information derived from the day after the first awakening relative to what happened the following night.
When there was a second night with awakening, there was a significant increase in symptom code (1.42 to 1.64, p=0.01), puffs of albuterol used for symptoms per day (3.01 to 3.71, p=0.05), and a decrease in evening peak flow (83.9 percent to 77.5 percent personal best, p=0.01) relative to days after isolated awakenings. This suggests that parents can use detailed information on the day after an awakening to help predict their child’s clinical course and make decisions about the need for increased observation.
Parents of children, especially adolescents who might disregard symptoms to continue with activities, need to be reminded about the importance of nocturnal awakenings and given specific instructions for response. Our data suggest that peak flows may help identify significant changes in clinical course.
1. Strunk R, Sternberg A, Bacharier L, Szefler S. Nocturnal awakening due to asthma in children with mild to moderate asthma in the Childhood Asthma Management Program. J Allergy Clin Immunol. 2002;110:395-403.
Dr. Strunk is the Strominger Professor of Pediatrics at Washington University School of Medicine, St. Louis. He’s also a member of the division of allergy and pulmonary medicine at St. Louis Children’s Hospital and director of the St. Louis centers for the Child Asthma Management Program and the Childhood Asthma Research and Education Network.
Nature of Nocturnal Asthma
Here are two examples of the importance of tracking nocturnal asthma. The first case represents the danger of ignoring nocturnal symptoms, even when these symptoms aren’t accompanied by a significant change in daytime symptoms. The second case represents an opportunity for early intervention.
A 12-year-old girl with known severe persistent asthma was on a regular high-dose inhaled corticosteroid, salmeterol, theophylline and as-needed short-acting bronchodilator. Oral steroids also were available at her home.
Her asthma had been well controlled for months. She saw an asthma specialist at regular intervals. During those visits, she learned the importance of early recognition of an exacerbation, of treating asthma regularly and of responding promptly to increased symptoms.
She was known to be allergic, with a signi.ficant sensitivity to Alternaria mold. In June, the weather became warm during the day and cool at night. Her family started sleeping with the windows open.
One night, she awakened at 2 a.m. and went to her mother to ask for help because of severe wheezing. She then lost consciousness. Her family called 9-1-1, and the paramedics found her with severe wheezing initially and then a respiratory arrest. They intubated her at home.
Upon arrival at the hospital, her arterial blood gas showed a pH of 6.9 and a pCO2 over 100. She responded to treatment and was extubated within 24 hours.
Upon recovery, further history obtained from the patient indicated that she had awakenings on each of the previous three nights before the final episode. On all of these occasions, she had used her inhaler without notifying her parents. She had continued to be active during the day with only mild asthma difficulties. Apparently, she had been regularly taking her medications.
This case demonstrates the severe consequences of nighttime awakenings, especially when consecutive awakenings occur and treatment isn’t changed in response to the awakenings. Further, it reveals a classic problem of a patient who disregards the risk of death due to asthma; the patient continued her end-of school activities and didn’t notify her parents of her increased symptoms.
The second case is an 8-year-old boy with known severe persistent asthma who was on high-dose inhaled corticosteroids, leukotriene modifiers and long-acting bronchodilators. He had developed very mild upper respiratory symptoms at the same time that his mother had a cold. He remained well, playing actively and going to school without limitations.
He went to bed without difficulty but awakened at 3 a.m. with sudden onset wheezing. His mother administered albuterol, and he returned to sleep. Later, the child awoke with more wheezing and required an additional bronchodilator treatment.
His symptoms improved, but the peak flow after this albuterol treatment was only 60 percent of his personal best. His mother contacted the physician on call for advice, and oral steroids were started with regular albuterol for the next 48 hours.
The second case represents awakenings that occur essentially without warning. In the Childhood Asthma Management Program data, we didn’t find the hoped-for early warning signs that could alert parents of a first awakening. However, we did find evidence that paying close attention the day after an awakening can help predict a second awakening and thus the start of a significant exacerbation.
—Robert C. Strunk, MD