Perception of dyspnea during acetylcholine-induced bronchoconstriction in asthmatic children

doi:10.1016/S1081-1206(10)60241-4

Annals of Allergy, Asthma & Immunology

Volume 102, Issue 2, February 2009, Pages 121-124

https://doi.org/10.1016/S1081-1206(10)60241-4 Get rights and content

Background

Few studies have examined the relationship between dyspnea perception and bronchial hyperresponsiveness (BHR) in asthmatic children.

Objective

To test the hypothesis that severe BHR is associated with poor perception of the severity of airway obstruction.

Methods

One hundred one asthmatic children (mean [SD] age, 11.1 [2.3] years) were evaluated using acetylcholine chloride (Ach) challenge. The BHR was assessed as the provocative concentration of Ach causing a 20% decrease in forced expiratory volume in 1 second (FEV₁) (PC₂₀). Perception of dyspnea was scored using a modified Borg scale after each dose of Ach and bronchodilator. The dyspnea threshold was defined as the point at which the Borg scale score became higher than 0. We evaluated the dyspnea perception score at a 20% decrease in FEV₁ relative to baseline (PS₂₀) and after bronchodilator administration (PS_BD).

Results

The mean (SD) PS₂₀ and PS_BD were significantly lower in the severe vs the mild BHR group (PS₂₀: 2.1 [1.9] vs 4.2 [2.4], P < .001; PS_BD: 0.5 [1.0] vs 1.0 [1.3], P = .048). The mean (SD) % decrease in FEV₁ at the dyspnea threshold was significantly greater in the severe vs the mild BHR group (14.1% [11%] vs 5.4% [11%], P < .001). The PS₂₀ was correlated positively with the PC₂₀ (r² = 0.25, P < .001), and the decrease in FEV₁ at the dyspnea threshold was correlated negatively with the PC₂₀ (r² = 0.18, P < .001).

Conclusions

Moderate to severe asthmatic children with severe BHR perceive dyspnea only after the stage of mild bronchoconstriction has passed. This relative insensitivity to dyspnea in asthmatic children with severe BHR may lead to undertreatment of asthma.

Section snippets

INTRODUCTION

Bronchial asthma accounts for most children with dyspnea. In recent years, asthma has become an increasingly common disease, afflicting approximately 5% of the general population.¹ There is good evidence of a significant increase in asthma prevalence in some countries. The annual number of deaths worldwide from asthma has been estimated to be 250,000.² It seems that many patients who die of acute severe asthma may initially underestimate the severity of their asthma episode.³ They tend to use

Patients

One hundred one children (6–15 years of age; 54 boys and 47 girls) diagnosed as having asthma were recruited from the outpatient division of the Department of Pediatrics of the National Hospital Organization, Fukuoka National Hospital. All the children satisfied the criteria for the diagnosis of bronchial asthma proposed in the Global Initiative for Asthma guidelines.¹ All the patients were clinically stable (ie, had no history of viral infections or asthma attacks during at least the week

RESULTS

One hundred one children were evaluated by means of the Ach challenge test, including 55 with severe BHR (PC₂₀ <2.5 mg/mL) and 46 with mild BHR (PC₂₀ ≥2.5 mg/mL). The characteristics of the patients are summarized in Table 1. The 2 subgroups were similar in terms of mean age, prevalence of treatment with ICSs, and lung functions at baseline. The FeNO level was significantly higher in the severe BHR group than in the mild BHR group (P < .001).

The scores on the Borg scale and the decrease in FEV₁

DISCUSSION

In this study, asthmatic children with severe BHR exhibited reduced perception of the sense of dyspnea. These results reveal that asthmatic children with severe BHR and a high FeNO level begin to perceive their dyspnea only after the asthmatic bronchoconstriction becomes relatively severe compared with those with mild BHR and a lower FeNO level. Significant positive correlations were found with FeNO level and the sputum eosinophilia and other markers of eosinophilic inflammation in the sputum.⁹

ACKNOWLEDGMENTS

We thank Hiroko Nogami, MD, PhD, Yoko Murakami, MD, Yoshio Moriyasu, MD, Natsuko Masumoto, MD, Naoyuki Kando, MD, Naohiko Taba, MD, Daisuke Hayashi, MD, Yuko Amimoto, MD, and the staff of the Fukuoka National Hospital for their help.

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History may be limited in critically ill patients, but if able to obtain, history should include time of symptom onset, precipitating cause, symptom severity compared to prior exacerbations, and treatments attempted prior to ED presentation [9,10,14,17,27,28]. Clinicians should screen for symptoms that suggest an alternate etiology, such as anaphylaxis, congestive heart failure, pneumonia, and pulmonary embolism, as well as other conditions that may result in wheezing and respiratory distress (Table 1) [29–49]. Increasing use of short-acting beta agonist therapy, recent glucocorticoid use, recent ED visit or hospital admission for asthma, and any prior airway interventions for asthma (e.g., non-invasive positive pressure ventilation [NIPPV] and endotracheal intubation) may suggest a more severe exacerbation [9,10,14,17,27,28].
Asthma is a common reason for presentation to the Emergency Department and is associated with significant morbidity and mortality. While patients may have a relatively benign course, there is a subset of patients who present in a critical state and require emergent management.
This narrative review provides evidence-based recommendations for the assessment and management of patients with severe asthma.
It is important to consider a broad differential diagnosis for the cause and potential mimics of asthma exacerbation. Once the diagnosis is determined, the majority of the assessment is based upon the clinical examination. First line therapies for severe exacerbations include inhaled short-acting beta agonists, inhaled anticholinergics, intravenous steroids, and magnesium. Additional therapies for refractory cases include parenteral epinephrine or terbutaline, helium‑oxygen mixture, and consideration of ketamine. Intravenous fluids should be administered, as many of these patients are dehydrated and at risk for hypotension if they receive positive pressure ventilatory support. Noninvasive positive pressure ventilation may prevent the need for endotracheal intubation. If mechanical ventilation is required, it is important to avoid breath stacking by setting a low respiratory rate and allowing permissive hypercapnia. Patients with severe asthma exacerbations will require intensive care unit admission.
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Perception of bronchodilation assessed by Visual Analogue Scale in children with asthma
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However, there was no significant relationship between VAS and age of children. The perception of breathlessness has been investigated by several studies in children,21–27 but most of them were conducted in “experimental” settings, such as in patients with symptoms experimentally induced by bronchoconstrictor stimuli (such as methacholine, histamine, or exercise) also considering an ethnical aspect.20 Only one study was conducted in a real-life condition, such as considering the asthma symptoms perception assessed by VAS during a regular consultation in an outpatient clinic, where children with asthma were referred for the asthma diagnosis confirmation.18
Visual Analogue Scale (VAS) has been proposed as a useful tool for assessing the perception of asthma symptoms, a cornerstone in disease management. While airway flow limitation and its reversibility are thought to be a useful marker of disease severity, there are very few studies that evaluated the response to bronchodilation (BD) testing perception by VAS. To investigate whether VAS assessment of breathlessness perception could provide a useful tool to assess the response to BD testing in asthmatic children.
This cross-sectional study included a total of 150 children (96 males, mean age 11.05 years) with asthma, 50 had bronchial obstruction (i.e. FEV₁ <80% of predicted). Perception of breathlessness was assessed by VAS; lung function was measured by spirometry. BD testing was performed in all children.
In children with bronchial obstruction, VAS at baseline was 4.7 and significantly increased to 6.9 (p < 0.001) after BD. In children without bronchial obstruction, VAS at baseline was 7.4, but further significantly increased to 8.4 after BD testing (p < 0.01). There was a significant difference in Δ VAS between children with bronchial reversibility and children without it (p < 0.0001).
The present study demonstrates that VAS might be considered an initial tool to assess the BD response in children with asthma, mainly with overt bronchial obstruction.
Asthma outcomes: Symptoms
2012, Journal of Allergy and Clinical Immunology
Citation Excerpt :
Thus airflow obstruction was considerably more severe in a subgroup of study participants than in other studies of children (eg, studies of mild persistent asthma in which the FEV1 is over 93% predicted value [Childhood Asthma Management Program and Personalized Assessment and Control Tool]).11,13 The lower FEV1 in this subgroup of participants may help explain why symptom scores were not associated with FEV1: there is evidence that blunted perception of airflow obstruction occurs in patients with more severe disease.8,14 All 3 daytime symptom questionnaires discriminated between stable and new-onset/worse groups at baseline, but the short duration of the trial was insufficient for evaluation of longitudinal validity.
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Asthma symptom instruments were classified as daily diaries (prospectively recording symptoms between research visits) or retrospective questionnaires (completed at research visits). We conducted a systematic search in PubMed and a search for articles that cited key studies describing development of instruments. We classified outcome instruments as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011.
Four instruments (3 daily diaries, 1 for adults and 2 for children; and 1 retrospective questionnaire for adults) were identified. Minimal clinically important differences have not been established for these instruments, and validation studies were only conducted in a limited number of patient populations. Validity of existing instruments may not be generalizable across racial-ethnic or other subgroups.
An evaluation of symptoms should be a core asthma outcome measure in clinical research. However, available instruments have limitations that preclude selection of a core instrument. The working group participants propose validation studies in diverse populations, comparisons of diaries versus retrospective questionnaires, and evaluations of symptom assessment alone versus composite scores of asthma control.
Predictive factors for airway hyperresponsiveness in children with respiratory symptoms
2011, Annals of Allergy, Asthma and Immunology
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Our data also showed that dyspnea, particularly exercise-induced dyspnea, was found to be more frequent in patients without AHR. In parallel to our findings, several studies16,17 have reported poor perception of dyspnea or exercise-induced dyspnea among children with AHR and asthma. Moreover, van Gent et al18 reported that perception of dyspnea was worse in children with undiagnosed asthma with AHR than in children with physician-diagnosed asthma.
Asthma diagnosis is a challenging condition, particularly in patients without obstructive pattern and reversibility on spirometry. Determination of airway hyperresponsiveness (AHR) may be helpful, but the procedure is time-consuming and not always practical.
To determine the potential factors that may predict the presence of AHR in children with asthmalike symptoms but without obstructive pattern and reversibility on spirometry.
All patients with asthmalike symptoms but without obstructive pattern and reversibility on spirometry were analyzed retrospectively between January 9, 2007, and December 30, 2009. The features of clinical history and laboratory results were analyzed with univariate and multivariate regression analysis.
A total of 111 children between 6 and 18 years of age, with a median age of 10.2 years, were analyzed, and AHR was detected in 67 patients (60.3%). Multivariate logistic regression analysis revealed coexistence of nocturnal cough and exercise-induced cough (odds ratio [OR], 22.1; 95% confidence interval [CI], 3.1–159.2; P = .004), eosinophilia (OR, 18.7; 95% CI, 1.9–178.7; P = .01), and borderline bronchodilator response in forced expiratory volume in 1 second (between 7% and 11%) (OR, 10.1; 95% CI, 2.1–49.1; P = .004) as significant risk factors for the presence of AHR, whereas exercise-induced dyspnea was found to be related to the absence of AHR (OR, 0.2; 95% CI, 0.1–0.8; P = .02).
In children with asthmalike symptoms but with normal spirometry, certain features of clinical history and laboratory results can strongly predict the presence of AHR and may help less frequent use of challenge tests.
Prediction of peak flow values followed by feedback improves perception of lung function and adherence to inhaled corticosteroids in children with asthma
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Under-perception of respiratory compromise is a risk factor for emergency department (ED) visits, hospitalisations, near-fatal and fatal asthma attacks in children.1 Children with severe bronchial hyperresponsiveness are particularly at risk for missing the early stage of bronchoconstriction during asthma exacerbations.2 A window of opportunity exists when patients with asthma can use bronchodilator medications in the days leading up to a severe asthma exacerbation and prevent its onset.3 4
Failure to detect respiratory compromise can lead to emergency healthcare use and fatal asthma attacks. The purpose of this study was to examine the effect of predicting peak expiratory flow (PEF) and receiving feedback on perception of pulmonary function and adherence to inhaled corticosteroids (ICS).
The sample consisted of 192 ethnic minority, inner-city children (100 Puerto Rican, 54 African-American, 38 Afro-Caribbean) with asthma and their primary caregivers recruited from outpatient clinics in Bronx, New York. Children's PEF predictions were entered into an electronic spirometer and compared with actual PEF across 6 weeks. Children in one study were blinded to PEF (n=88; no feedback) and children in a separate study were able to see PEF (n=104; feedback) after predictions were locked in. Dosers were attached to asthma medications to monitor use.
Children in the feedback condition displayed greater accuracy (p<0.001), less under-perception (p<0.001) and greater over-perception (p<0.001) of respiratory compromise than children in the no feedback condition. This between-group difference was evident soon after baseline training and maintained across 6 weeks. The feedback condition displayed greater adherence to ICS (p<0.01) and greater quick-relief medication use (p<0.01) than the no feedback condition.
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Original Articles: Asthma, Lower Airway DiseasesPerception of dyspnea during acetylcholine-induced bronchoconstriction in asthmatic children

Background

Objective

Methods

Results

Conclusions

Section snippets

INTRODUCTION

Patients

RESULTS

DISCUSSION

ACKNOWLEDGMENTS

Chest

Chest

The global burden of asthma: executive summary of the GINA Dissemination Committee report

Allergy

Perception of intrinsic and extrinsic respiratory loads in children with life-threatening asthma

Pediatr Pulmonol.

Treatment patterns among adult patients with asthma: factors associated with overuse of inhaled β-agonists and underuse of inhaled corticosteroids

Arch Intern Med.

Flow-volume curve in healthy and asthmatic children [in Japanese]

Rinsho To Kenkyu

Measurement of exhaled nitric oxide in children, 2001

Eur Respir J.

Original Articles: Asthma, Lower Airway Diseases
Perception of dyspnea during acetylcholine-induced bronchoconstriction in asthmatic children