Discrepancy between clinical asthma control assessment tools and fractional exhaled nitric oxide

doi:10.1016/S1081-1206(10)60199-8

Annals of Allergy, Asthma & Immunology

Volume 101, Issue 2, August 2008, Pages 124-129

https://doi.org/10.1016/S1081-1206(10)60199-8 Get rights and content

Background

Asthma is an inflammatory disease, yet clinical tools that evaluate asthma control do not include measures of inflammation.

Objective

To determine the correlation between fractional exhaled nitric oxide (FeNO) and each of 5 asthma control evaluation tools, namely, the Asthma Control Questionnaire (ACQ), the Asthma Control Test (ACT), the National Asthma Education and Prevention Program (NAEPP) goals of therapy, the Joint Task Force Practice Parameter (JTFPP) on attaining optimal asthma control, and the Global Initiative for Asthma (GINA) guidelines.

Methods

Patients 6 years or older who had asthma were clinically evaluated by an asthma specialist. Patients completed the ACT and ACQ and underwent spirometry and FeNO measurement. The physician was blinded to FeNO results until asthma control assessments were concluded. Correlations between FeNO level and each clinical evaluation tool were calculated.

Results

One hundred patients 6 to 86 years old were enrolled. No significant association was found between FeNO level and asthma control based on ACQ (P > .99), ACT (P = .53), NAEPP (P = .53), JTFPP (P = .30), or GINA (P = .86) criteria. Agreement was high among the NAEPP, the JTFPP, and GINA; moderate between the ACQ and the ACT; and poor to fair between the ACT or the ACQ and the other 3 tools.

Conclusions

In addition to clinical evaluation, the incorporation of FeNO measurement in evaluating asthma is likely to lead to a more optimal pharmacotherapy, guidance in adjusting the dosage of anti-inflammatory agents, and positive long-term disease outcome.

Section snippets

INTRODUCTION

Airway inflammation is central to the pathogenesis of asthma and can lead to airway remodeling and irreversible impairment of lung function.¹ Asthma control guidelines stress the importance of anti-inflammatory medications, particularly inhaled corticosteroids (ICS), as first-line treatment.² In assessing asthma control, it would be prudent to include markers of airway inflammation.

Current asthma control evaluation tools are primarily clinical parameters (eg, daytime and nocturnal

Study Population

Patients (scheduled and walk-ins) who were presenting to an allergy and asthma clinic were enrolled in the study. Patients 6 years or older with specialist-diagnosed asthma were eligible for participation. Patients were excluded if they had any of the following: respiratory tract infection within the preceding 14 days, tobacco smoking during the preceding 30 days, or atopic dermatitis. Respiratory tract infections¹⁸ and atopic dermatitis¹⁹ have been shown to increase FeNO, whereas tobacco

Patient Demographics

One hundred patients 6 to 86 years old (15 patients ≤12 years) were enrolled; 65% were white and 34% were African American (Table 3). Twenty-six percent of patients were ex-smokers, with a mean (SD) smoke-free duration of 18 (13) years. A positive skin prick test result to 1 or more aeroallergens was noted in 93.7%, and allergic rhinitis was diagnosed in 59%. Most patients (81%) were taking ICS either as monotherapy or in combination with long-acting β₂-agonists and/or leukotriene antagonists.

Correlation Between FeNO and Clinical Evaluation Tools

DISCUSSION

This study indicates that commonly used asthma control evaluation tools do not accurately reflect the status of airway inflammation as reflected by FeNO. Use of such tools may lead to inappropriate clinical decision making and result in suboptimal short-term and long-term care.

Several studies showed that asthma control cannot be optimally evaluated by any single parameter, particularly the patient's perception.²⁶ Other parameters viewed as objective, such as asthma exacerbations and SABA use,

REFERENCES (42)

RA Nathan et al.
Development of the asthma control test: a survey for assessing asthma control
J Allergy Clin Immunol
(2004)
RC Strunk et al.
Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children
J Allergy Clin Immunol
(2003)
AW Murphy et al.
Respiratory nitric oxide levels in experimental human influenza
Chest
(1998)
F Balboa De Paz et al.
Exhaled nitric oxide in healthy and asthmatic children [in Spanish]
An Esp Pediatr
(2002)
AC Olin et al.
Increased nitric oxide in exhaled air after intake of a nitrate-rich meal
Respir Med.
(2001)
AH Liu et al.
Development and cross-sectional validation of the Childhood Asthma Control Test
J Allergy Clin Immunol
(2007)
RH Green et al.
Asthma exacerbations and sputum eosinophil counts: a randomized controlled trial
Lancet
(2002)
JM Sippel et al.
Exhaled nitric oxide levels correlate with measures of disease control in asthma
J Allergy Clin Immunol
(2000)
SL Limb et al.
Irreversible lung function deficits in young adults with a history of childhood asthma
J Allergy Clin Immunol
(2005)
EF Juniper et al.
Identifying “well-controlled” and “not well-controlled” asthma using the Asthma Control Questionnaire
Respir Med.
(2006)

S Vahlkvist et al.

Daily home measurements of exhaled nitric oxide in asthmatic children during natural birch pollen exposure

J Allergy Clin Immunol

(2006)

J Bousquet et al.

Asthma: from bronchoconstriction to airways inflammation and remodeling

Am J Respir Crit Care Med.

(2000)

National Asthma Education and Prevention Program

Guidelines for the diagnosis and management of asthma: update 2002

J Allergy Clin Immunol

(2002)

EF Juniper et al.

Development and validation of a questionnaire to measure asthma control

Eur Respir J.

(1999)

JT Li et al.

Attaining optimal asthma control: a practice parameter

J Allergy Clin Immunol

(2005)

Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Washington, DC: US...

J Bousquet et al.

Eosinophilic inflammation in asthma

N Engl J Med.

(1990)

GP Currie et al.

Does bronchial hyperresponsiveness in asthma matter?

J Asthma

(2004)

DNR Payne et al.

Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in children with difficult asthma, after treatment with oral prednisolone

Am J Respir Crit Care Med.

(2001)

TJ Warke et al.

Exhaled nitric oxide correlates with airway eosinophils in childhood asthma

Thorax

(2002)

A Jatakanon et al.

Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma

Thorax

(1998)

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Citation Excerpt :
Poor attendance at office visits may be further exacerbated by poor symptom self-perception, as nearly 10% of pregnant women with uncontrolled asthma misclassify their asthma as mild.25 In other underserved, albeit nonpregnant populations, subjective symptoms have been shown to poorly correlate with objective measurements of asthma control, which may further support difficulty in self-perception of asthma severity as a contributing barrier to optimal asthma management.29,30 Thus, patient outreach outside the office setting may have promise in improving asthma care in underserved communities.31
Phenotypes favoring fractional exhaled nitric oxide discordance vs guideline-based uncontrolled asthma
2019, Annals of Allergy, Asthma and Immunology
Despite potential value of identification of allergic inflammation with fractional exhaled nitric oxide (FeNO) in managing asthma, randomized clinical trials have not consistently shown better outcomes compared with guideline management alone.
To assess the effectiveness of FeNO vs non–FeNO-based therapeutic algorithms in managing asthma, and the phenotypic profile associated with FeNO >35 ppb yet well controlled by guidelines, as a potential model to predict better FeNO-based algorithm outcomes.
This is a randomized controlled study (RCT) in 88 high-risk children with asthma 7 to 18 years of age across 352 visits over a 1-year period. Generalized estimating equations analysis assessed algorithm group differences in outcomes and characteristics associated with higher odds uncontrolled by FeNO alone in the treatment decision algorithm.
The FeNO treatment algorithm did not show superiority in reducing exacerbations and morbidity (P > .05). Phenotypes that more than doubled the odds FeNO alone identified uncontrolled asthma included adolescence, non-adherence, high atopy (>6+), and baseline FeNO >35 ppb, whereas obesity, FEF_25-75% < 65% predicted, and bronchodilator response >10% decreased the odds. Uncontrolled asthma by FeNO alone (F) vs guidelines alone (G) showed overall F/G > 1.0 in adolescents, but <1.0 in younger patients unless the FeNO threshold was reduced to >20 ppb.
Our study suggests that age and phenotypes play a key role in FeNO discordance compared with the conventional guideline-based uncontrolled asthma. The FeNO-based therapeutic algorithm, if confirmed further, could provide the clinician with an effective asthma management tool. The clinical implication could improve future FeNO-based RCTs and treatment decision algorithms in managing asthma by considering phenotypes and age-dependent FeNO thresholds.
Comparing Asthma Control Questionnaire (ACQ) and National Asthma Education and Prevention Program (NAEPP) asthma control criteria
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Adequate assessment of control is critical to asthma management. The Asthma Control Questionnaire (ACQ) and the National Asthma Education and Prevention Program (NAEPP) criteria are commonly used measures of asthma control.
To examine the associations between the ACQ and NAEPP criteria and compare the validity in association with lung function, asthma exacerbation, and quality of life.
The ACQ and the NAEPP criteria were administered to 373 adolescents with asthma aged 12 to 20 years. The 2 measures correlated with forced expiratory volume in 1 second (FEV₁), asthma exacerbation (oral corticosteroid use, hospitalization, and emergency department [ED] use) in the past 12 months, and quality of life.
Agreement between the ACQ and NAEPP criteria was moderate (κ = 0.40-0.61). Neither of the 2 measures was a reliable predictor of FEV₁ less than 80% because of the high rate of false-positive results for the ACQ (68%) and low sensitivity for the NAEPP (49%). The NAEPP identified more cases of uncontrolled asthma (84.6%) than the ACQ (64.6%). The ACQ was a significant predictor of recent oral corticosteroid use, hospitalization, and ED visits (area under the curve = 0.66, 0.66, and 0.64, respectively; P < .001), as was NAEPP (area under the curve = 0.63, 0.66, and 0.61, respectively; P < .001). Both measures were significantly associated with quality of life, and the associations were particularly strong for the ACQ (r = −0.87 for symptom subscale, r = −0.76 for activity subscale, and r = −0.78 for emotional function subscale).
Neither the ACQ nor the NAEPP appears to reliably predict lung function, whereas both measures reasonably associate with acute asthma exacerbation. The ACQ may be the superior measure in gauging the psychosocial effect of asthma control given its particularly strong associations with quality of life.
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: Disclosures: Dr Boggs is performing research studies supported by Aerocrine Inc and Apieron.

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Original Articles: Asthma, Lower Airway DiseasesDiscrepancy between clinical asthma control assessment tools and fractional exhaled nitric oxide

Background

Objective

Methods

Results

Conclusions

Section snippets

INTRODUCTION

Study Population

Patient Demographics

Correlation Between FeNO and Clinical Evaluation Tools

DISCUSSION

J Allergy Clin Immunol

J Allergy Clin Immunol

Chest

An Esp Pediatr

Respir Med.

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

Respir Med.

J Allergy Clin Immunol

Asthma: from bronchoconstriction to airways inflammation and remodeling

Am J Respir Crit Care Med.

Guidelines for the diagnosis and management of asthma: update 2002

J Allergy Clin Immunol

Development and validation of a questionnaire to measure asthma control

Eur Respir J.

Attaining optimal asthma control: a practice parameter

J Allergy Clin Immunol

Eosinophilic inflammation in asthma

N Engl J Med.

Does bronchial hyperresponsiveness in asthma matter?

J Asthma

Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in children with difficult asthma, after treatment with oral prednisolone

Am J Respir Crit Care Med.

Exhaled nitric oxide correlates with airway eosinophils in childhood asthma

Thorax

Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma

Thorax

Original Articles: Asthma, Lower Airway Diseases
Discrepancy between clinical asthma control assessment tools and fractional exhaled nitric oxide