Fatigue associated with severe asthma in children
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Key takeaways:
- The questionnaire assessed general fatigue, sleep-rest fatigue and cognitive fatigue.
- Asthma-related quality of life, symptom control and comorbid breathing were most associated with fatigue.
Four out of 10 children and adolescents with severe asthma also experienced high levels of fatigue, with poorer asthma-related quality of life, according to a study published in Pediatric Allergy and Immunology.
Multiple clinical factors and patient-reported outcomes were associated with this fatigue, Susanne Vijverberg, MSc, PhD, assistant professor, pulmonary medicine and pediatric pulmonology, Amsterdam UMC, and colleagues wrote.
“This study question was prompted by patients and their families,” Vijverberg told Healio.
The patients treated in the researchers’ hospital and in their youth council, as well as patient organizations such as Lung Foundation Netherlands, which funded this study, have stressed that fatigue is a common symptom, she continued.
“However, there is not much known about fatigue and asthma,” she said. “It is rarely studied, especially in children. It is a symptom that easily gets overshadowed by other asthma symptoms that might be more visible, such as coughing and wheezing.”
Also, the researchers wrote, clinical practices do not routinely monitor it, and clinical guidelines often do not cover fatigue or symptoms related to fatigue.
“Our study underscores the need to address fatigue as an integral part of asthma care,” Vijverberg said.
Study design, results
The researchers examined data from 78 children (64.1% boys) in the Pediatric Asthma Non-Invasive Diagnostic Approaches multi-center prospective observational cohort study of Dutch children aged 6 to 17 years diagnosed with severe asthma.
Participants had a mean age of 11.8 years, and 55% had controlled asthma based on Asthma Control Test (ACT) or Childhood ACT (C-ACT) scores of 20 or higher.
Also, 52% had experienced an asthma attack in the prior 12 months, 73.1% had allergic rhinitis, 51.3% had atopic eczema and 32.1% had dysfunctional breathing.
For comparison, the researchers also examined data collected by Gordijin and colleagues from 328 children (44.8% boys; mean age, 11.8 years; 11.6% with a chronic disease) in a general population from daycare facilities and schools in the Netherlands.
Mean Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL-MFS) scores included 68.4 for the asthma group and 76.9 for the general population, with lower scores indicating more fatigue.
The general population also consistently had higher mean scores than the asthma group in the PedsQL-MFS’s general fatigue (80.1 vs. 70.9), sleep-rest fatigue (74.6 vs. 66.2) and cognitive fatigue (76.1 vs. 68.1) domains.
More specifically, 28.2% were fatigued and 15.4% were severely fatigued in the asthma group, and 14% were fatigued and 3.4% were severely fatigued in the general population based on overall PedsQL-MFS results, with similar differences by domain.
The occurrence of one or more asthma attacks in the prior 12 months had a significant effect on total fatigue levels (beta = –0.22; P < .05; delta R2 = 0.04), with the greatest impact in the sleep-rest fatigue domain (beta = –0.35; P < .01; delta R2 = 0.12).
In the asthma group, the researchers also noted independent associations between higher fatigue levels and:
- comorbid dysfunctional breathing: beta = –0.36; P < .01; delta R2 = 0.12;
- obstructive sleep apnea syndrome: beta = –0.33; P < .01; delta R2 = 0.1;
- gastroesophageal reflux: beta = –0.3; P < .01; delta R2 = 0.9; and
- nasal corticosteroid use: beta = –0.22; P < .05; delta R2 = 0.05.
The researchers also noted associations between antihistamine use and sleep-rest fatigue (beta = –0.26; P < .05; delta R2 = 0.06) and between FEV1/FVC z scores and cognitive fatigue (beta = 0.24; P < .05; delta R2 = 0.06).
However, the researchers continued, there were no associations between fatigue levels and inhaled corticosteroid dosage or maintenance oral corticosteroid use.
The researchers also found independent associations between asthma symptom control and total fatigue score (beta = 0.56; P < .01; delta R2 = 0.24), significantly between control and general fatigue (beta = 0.55; P < .01; R2 = 0.23), sleep-rest fatigue (beta = 0.45; P < .01; delta R2 = 0.16), and cognitive fatigue (beta = 0.39; P < .01; R2 = 0.14).
There were independent associations between total fatigue scores and asthma-related quality of life as well (beta = 0.77; P < .01; delta R2 = 0.43), with fatigue accounting for approximately 43% of the variance in Pediatric Asthma Quality of Life Questionnaire scores.
Significant associations persisted between the individual fatigue domains and asthma-related quality of life as well.
There were no significant differences in fatigue scores between the children with asthma who participated during the COVID-19 pandemic (n = 38) and those who participated after the pandemic was over (n = 40).
Conclusions, next steps
Noting that this was the first study to demonstrate how common fatigue is among children with severe asthma, the researchers concluded that fatigue is more prevalent among this population compared with the general population.
“An important step towards better asthma outcomes is recognition for fatigue to be a common symptom in children with severe asthma,” Vijverberg said. “There should be more awareness that fatigue can have a large impact on children’s lives.”
The researchers cautioned that high levels of fatigue could limit how children participate in daily life, influencing their development and transition into adulthood. But improving disease control and minimizing symptoms may reduce fatigue and improve quality of life, they continued.
“There is a need for tools to monitor fatigue severity and impact and identify those children most affected,” Vijverberg said.
Further, the researchers said that fatigue among these children probably is due to physical and psychosocial challenges in addition to the biological side effects of asthma and its treatment, so interventions should be tailored to each child’s individual needs.
Such interventions may include lifestyle modifications, treatment targeting asthma control, psychosocial support and cognitive behavioral therapy, the researchers continued, adding that strategies used in other pediatric diseases may help as well.
“A multidisciplinary approach — involving, for example, pediatric pulmonologists, physiotherapist, psychologist and asthma nurses — could subsequently help to manage fatigue in severe asthma patients and improve asthma outcomes,” Vijverberg said.
In the future, the researchers advised, studies should determine the best approach for screening children with asthma for fatigue to reduce high levels, prevent its escalation and improve quality of life for these patients.
“Future studies are needed to determine the best approach to monitor fatigue as well as successful interventions to reduce the burden of fatigue in children with asthma,” Vijverberg said.
For more information:
Susanne Vijverberg, MSc, PhD, can be reached at s.j.vijverberg@amc.uva.nl.
Perspective
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The findings are not surprising, but they are significant and could impact practice. Patient-reported outcomes should help guide therapy, and implementing tools similar to the Pediatric Asthma Quality of Life Questionnaire and Asthma Control Test to assess the impact of treatment on patient-reported fatigue would help improve care.
Exercise intolerance is a known symptom for poorly controlled asthma. The Prevention and Incidence of Asthma and Mite Allergy study noted similar results and a possible mechanism of action such as reduced sleep secondary to nighttime symptoms as a cause for daytime fatigue. Villa and colleagues noted reduced aerobic capacity and endurance in children with severe persistent asthma.
Doctors should consider assessing fatigue in addition to other symptoms to assess control and guide therapy decisions. Future work could evaluate the incorporation of standardized assessment of fatigue in clinical care, especially as a patient-centered outcome.
Also, understanding that asthma plays a role in daytime fatigue may incentivize adolescents to adhere to their daily asthma therapy, especially for those who are active in school sports.
A prospective evaluation of adding patient-reported fatigue to guide medication adjustment and subsequent improvement in fatigue in patients with severe persistent asthma would be an important next step.
References:
Van Maanen A, et al. Eur Respir J. 2013;doi:10.1183/09031936.00019412.
Villa F, et al. Arch Dis Child. 2011;doi:10.1136/adc.2011.212431.
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