Percentage Fall in FVC at the Provocative Concentration of Methacholine Causing a 20% Fall in FEV1 in Symptomatic Asthma and Clinical Remission During Adolescence

doi:10.1378/chest.129.2.272

Chest

Volume 129, Issue 2, February 2006, Pages 272-277

https://doi.org/10.1378/chest.129.2.272 Get rights and content

Background

Many children with asthma go into long-term clinical remission at adolescence, but bronchial hyperresponsiveness (BHR) persists in approximately one half of these subjects. BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV₁ (PC₂₀). The percentage fall in FVC at the PC₂₀ (ΔFVC) has been suggested to be a more useful index of disease severity in asthma than PC₂₀.

Study objective

The aim of this study was to determine whether ΔFVC is higher in adolescents with symptomatic asthma than in those with clinical remission.

Patients and methods

Forty adolescents with symptomatic asthma and 80 adolescents with asthma remission underwent methacholine challenge testing. ΔFVC and PC₂₀ were measured on the methacholine dose-response curve.

Results

The mean (95% confidence interval [CI]) ΔFVC (15.5% [95% CI, 14.1 to 16.9%]) in the symptomatic group (n = 40) was significantly higher (p = 0.017) than that (12.8% [95% CI, 11.5 to 14.1%]) in the BHR-positive (PC₂₀ < 16 mg/mL) remission group (n = 44) or that (11.5% [95% CI, 10.2 to 12.8%]) of the BHR-negative remission group (n = 36), with no difference between the two latter groups (p = 0.581). No significant correlation was found between ΔFVC and PC₂₀ in the symptomatic group (r = − 0.156, p = 0.336) or in the whole remission group (r = − 0.187, p = 0.097).

Conclusions

Adolescents with symptomatic asthma had a higher ΔFVC than those with clinical remission, irrespective of the presence of BHR in the latter group. This finding suggests that ΔFVC may serve as an adjunct marker for differentiating between asthma persistence and remission during adolescence.

Section snippets

Materials and Methods

A group of adolescents (aged 13 to 17 years) with current atopic asthma was recruited from the allergy clinic at Seoul National University Children's Hospital. All subjects had a history of episodic wheezing and/or dyspnea, and had asthma diagnosed on the basis of airway reversibility (an increase in FEV₁ > 12% after bronchodilator administration) or PC₂₀ < 16 mg/mL. Atopy was defined as at least one positive skin-prick test result to a panel of 12 common airborne allergens in the presence of

Results

Forty patients with symptomatic asthma and 80 patients with asthma remission completed the study. Two subjects in the symptomatic group had a PC₂₀ > 16 mg/mL, but they were included in the study because they fulfilled the inclusion criteria. Of 80 subjects with asthma remission, 44 patients were found to have a PC₂₀ < 16 mg/mL (BHR-positive remission group), and the remaining 36 patients had a PC₂₀ > 16 mg/mL (BHR-negative remission group). The clinical characteristics of the three adolescent

Discussion

The present study shows that ΔFVC is higher in adolescents with symptomatic asthma than in those with asthma remission. This is unlikely to be due to a difference in PC₂₀ because ΔFVC was no different between the BHR-positive and BHR-negative remission groups and because no correlation was found between ΔFVC and PC₂₀.

In the present study, subjects were regarded to be in clinical remission when they reported the complete absence of symptoms and had received no treatment for at least 2 years

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Remission of asthma: The next therapeutic frontier?
2011, Pharmacology and Therapeutics
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The authors concluded that even in complete remission, asthma patients still exhibit a degree of airway inflammation and remodeling. A number of other studies have shown that abnormalities of airway function are detectable in patients with asthma remission, including AHR (Yoo et al., 2006), which may have a familial component (Koh et al., 2003). However, Koh et al. (Koh et al., 2002) showed that a plateau on the dose–response curve to high-dose inhaled methacholine (i.e. limited maximal airway narrowing) is more common in those with a clinical asthma remission than in subjects with current asthma symptoms.
Asthma treatment goals focus on disease control rather than remission as a therapeutic aim. This is in contrast to diseases where remission is frequently discussed and has well-defined criteria. In this review, we consider the similarities and differences between remission in asthma and another chronic inflammatory disease, rheumatoid arthritis, where new therapies have made remission a realistic treatment goal. Clinical remission of asthma is often defined as prolonged absence of asthma symptoms without requirement for medication while others insist on the demonstration of normal lung function and airway responsiveness. Even in those who develop a symptomatic remission of asthma, persistent physiological abnormalities and airway inflammation are common. There is a clear need to develop a precise, internationally accepted, definition of asthma remission that can be used as a therapeutic endpoint in studies of new asthma treatments. Spontaneous remission of asthma symptoms is relatively common, especially during adolescence. It is more likely in males, those with mild symptoms and normal lung function and in those who quit smoking, and may be linked to normalisation of immune function. Remission is less likely in severe asthma, atopy, eosinophilia, airflow obstruction, continued smoking and weight gain. Studies of spontaneous remissions may provide insight into how remission might be induced with therapy. Remission is not identical to cure, there remains a risk of subsequent symptomatic relapse of asthma and there is little evidence that current asthma treatments can induce remission. Long-term remission should be regarded as the next therapeutic frontier in asthma management.
Modifications in forced vital capacity during adenosine monophosphate-induced bronchoconstriction in asthma: Elationship with the response to ethacholine and the effect of inhaled corticosteroids
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The present results were derived from a cross-sectional study, and alternative explanations for differences in sFVC between patients treated and not treated with ICSs should be considered. First, it is known that histamine-induced declines in FVC are related to some extent to the baseline airway caliber. 32 Thus, the greater effect of methacholine on sFVC in the present patients taking ICSs compared with those not taking ICSs might be a consequence of differences in baseline FEV1.
The effect of adenosine monophosphate (AMP) on forced vital capacity (FVC) has never been systematically investigated.
To compare methacholine- and AMP-induced changes in FVC, as a marker of air trapping, in asthmatic patients treated and not treated with inhaled corticosteroids (ICSs).
Airway responsiveness to equipotent concentrations of AMP and methacholine was obtained in asthmatic patients treated (n = 32) and not treated (n = 18) with ICSs. The response was expressed by the provocation concentration of agonist that caused a decrease in forced expiratory volume in 1 second (FEV₁) of 20% (PC₂₀) and by the slope of the FVC values recorded at each step of the challenge against the corresponding FEV₁ values (sFVC).
Although methacholine and AMP PC₂₀ values were similar in patients treated and not treated with ICSs, the mean (95% confidence interval) methacholine sFVC (but not AMP sFVC) was higher in those treated with ICSs (0.91; 0.77-1.06) than in those not taking ICSs (0.69; 0.57-0.81; P = .03). No significant correlation was found between sFVC and PC₂₀ values obtained with either methacholine or AMP. Methacholine and AMP sFVC values were significantly related, but only in the group treated with ICSs (r = 0.60, P < .001).
Although the AMP-induced decline in FVC in asthmatic patients is similar to that observed with equipotent concentrations of methacholine, the apparently different effect of ICSs on changes in FVC induced by each agonist suggests that the information provided by the 2 bronchoconstrictor agents is not interchangeable and that the information generated by the analysis of the effect of each agonist on FEV₁ and FVC may be complementary.
Comparison of percentage fall in FVC at the provocative concentration of methacholine causing a 20% fall in FEV<inf>1</inf> between patients with asymptomatic bronchial hyperresponsiveness and mild asthma
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Unlike the PC20, ΔFVC was found to be significantly related to the average number of oral corticosteroid prescriptions per month, which suggests that it may be a more useful index of disease severity of asthma than PC20.818 We have shown that adolescents with symptomatic asthma have a higher level of ΔFVC than those with clinical remission, irrespective of PC20 levels in the latter group.24 The present study was based on the hypothesis that ΔFVC may reflect gas trapping due to excessive bronchoconstriction.8
A significant proportion of individuals who have no symptoms of asthma or other respiratory diseases show bronchial hyperresponsiveness (BHR). BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV₁ (PC₂₀). The percentage fall in FVC at the PC₂₀ (ΔFVC) has been suggested to reflect maximal airway response and to be a more useful index of disease severity in asthma than PC₂₀. The aim of this study was to investigate whether asymptomatic BHR would differ from symptomatic BHR with regard to ΔFVC.
Methacholine bronchial challenge tests were conducted in children with no past or current symptoms of asthma, allergic rhinitis, or other respiratory diseases, who were identified among siblings of children with asthma. Forty-three children with asymptomatic BHR (PC₂₀ < 16 mg/mL) were recruited, and 43 children with mild asthma who were matched for age, sex, and PC₂₀ were selected (mild asthma group). The ΔFVC on methacholine concentration-response curves was retrospectively analyzed in the two groups.
There were no differences in the frequency of atopy, blood eosinophil counts, serum IgE levels, and spirometric values between the asymptomatic BHR and mild asthma groups. Mean (± SD) ΔFVC was significantly (p = 0.005) lower in the asymptomatic BHR group (14.5 ± 3.6%) than in the mild asthma group (16.9 ± 4.3%).
Our results suggest that children with asymptomatic BHR have a lower level of maximal airway response than mild asthmatics with a similar degree of BHR. This may be a possible explanation for the lack of symptoms in subjects with asymptomatic BHR.
Based on what parameters is safe to discontinuate inhaled corticosteroids in children with asthma?
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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

This study was supported in part by the Alumni Research Fund of the Department of Pediatrics, Korea University College of Medicine, and by BK 21 Project for Medicine, Dentistry and Pharmacy, Seoul National University.

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Chest

Original ResearchPercentage Fall in FVC at the Provocative Concentration of Methacholine Causing a 20% Fall in FEV1 in Symptomatic Asthma and Clinical Remission During Adolescence

Background

Study objective

Patients and methods

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

J Allergy Clin Immunol

Chest

Respir Med

Respir Med

J Allergy Clin Immunol

Chest

Chest

Prognosis of asthma from childhood to adulthood

Am Rev Respir Dis

Evolution of asthma through childhood

Clin Exp Allergy

Airway responsiveness

Grading severity and treatment requirements to control symptoms in asthmatic children and their relationship with airway hyperreactivity to methacholine

Ann Allergy

Atopy, lung function and bronchial responsiveness in symptom-free paediatric asthma patients

Eur Respir J

Bronchial reactivity to inhaled histamine: a method and clinical survey

Clin Allergy

Original Research
Percentage Fall in FVC at the Provocative Concentration of Methacholine Causing a 20% Fall in FEV₁ in Symptomatic Asthma and Clinical Remission During Adolescence