Airway responsiveness to histamine as a test for overall severity of asthma in children

Murray, Andrew B.; Ferguson, Alexander C.; Morrison, Brenda J.

doi:10.1016/0091-6749(81)90169-x

Cited by 110 publications

(45 citation statements)

References 15 publications

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“…Asthma is a disease characterized by airway inflammation, hyperresponsiveness, and reversible airway obstruction, and the degree of airway hyperresponsiveness is related to the severity of the asthma symptoms [2, 3], the number of previous hospital admissions [4], and the treatment requirements [5]. For these reasons, the treatment of airway inflammation and hyperresponsiveness is essential for the management of asthma as well as for bronchodilating therapy.…”

Section: Discussionmentioning

confidence: 99%

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PACAP Reverses Airway Hyperresponsiveness Induced by Ozone Exposure in Guinea Pigs

Aizawa

Shigyo

Matsumoto³

et al. 1999

Respiration

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Background: We previously demonstrated that pituitary adenylate cyclase activating peptide (PACAP) inhibits airway smooth muscle contraction and plasma extravasation. Objective: We thus hypothesized that PACAP may regulate airway responsiveness through these effects and examined the effects of exogenously applied PACAP on the airway hyperresponsiveness induced by ozone exposure. Methods: Ozone exposure was carried out in awake, spontaneously breathing guinea pigs using 3 ppm for 2 h. Airway responsiveness to histamine was determined before and 30 and 90 min after the termination of ozone exposure for 2 h in anesthetized animals. Extravasation of Evans blue was measured before and 90 min after the termination of ozone exposure. Either PACAP (10^–6 mol/kg) or vehicle was administered intravenously 60 min after exposure. The airway responsiveness was expressed as the concentration of histamine required to produce a 200% increase in total pulmonary resistance (PC₂₀₀). Results: Ozone exposure caused a significant decrease in PC₂₀₀ (n = 5, p < 0.05) 30 min after ozone exposure which persisted 90 min thereafter, thus suggesting that ozone caused airway hyperresponsiveness. PACAP significantly suppressed the increase in airway hyperresponsiveness induced by ozone 90 min after exposure (n = 5, p < 0.05). In contrast, this peptide did not have any effect on plasma extravasation. Conclusion: We thus conclude that PACAP decreases ozone-induced airway responsiveness, and, therefore, intravenously administered PACAP may be useful in reversing airway hyperresponsiveness.

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Section: Discussionmentioning

confidence: 99%

“…It is, therefore, important to focus on the treatment of airway inflammation and hyperresponsiveness. The level of airway hyperresponsiveness usually correlates with the clinical severity of asthma [2, 3, 4, 5]. Therapeutic intervention which decreases airway hyperresponsiveness tends to reduce the severity of asthma.…”

Section: Introductionmentioning

confidence: 99%

PACAP Reverses Airway Hyperresponsiveness Induced by Ozone Exposure in Guinea Pigs

Aizawa

Shigyo

Matsumoto³

et al. 1999

Respiration

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“…The sensitivity of the airways to these agents is commonly expressed as a provocative concentration/dose causing a 20% fall (PC/D20) in forced expiratory volume in 1 s (FEV1). When exposed to high concentrations of inhaled histamine or methacholine, asthmatic patients show excessive narrowing of the airway, as reflected by an elevated or absent maximal response plateau [10][11][12] . Environmental influences and epigenetic mechanisms could pose important modifying factors shaping the asthma phenotype at the clinical level.…”

Section: Introductionmentioning

confidence: 99%

Possible control of paternal imprinting of polymorphisms of the ADAM33 gene by epigenetic mechanisms and association with level of airway hyperresponsiveness in asthmatic children

Kopřiva¹,

Godava²,

Marková³

et al. 2013

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Introduction. ADAM33 is the candidate gene most commonly associated with asthma and airway hyperreactivity (AHR). Aim. The aim of this study was to determine whether level of AHR is associated with certain alleles or haplotypes of the ADAM33 gene in asthmatic children. Methods. One hundred and nine asthmatic children and 46 controls from the general population were examined with spirometry before and after histamine and methacholine inhalation. All subjects were genotyped for single-nucleotide polymorphisms (SNPs) of the ADAM33 gene. Haplotypes were determined according to genotypes of the patient's parents. Results. We found the three most frequent ADAM33 haplotypes (a1-3) were associated with the highest level of AHR to methacholine and histamine in 66% of asthmatic children. The paternally transmitted GGGCTTTCGCA haplotype was seen in 73.3% asthmatic children with serious AHR to methacholine challenge (paternal and maternal origin of haplotype 73.3% to 37.5, P=0.046) Significant differences in the relative frequency of paternal haplotypes with high levels of AHR to histamine were found (P=0.013). Conclusion. ADAM33 haplotypes (a1, a2, a3) are associated with severity of AHR and are significantly more often transmitted in the paternal line.

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“…Bronchial hyperresponsiveness (BHR), measured as the provocation concentration (PC20) or dose (PD20) of inhaled histamine or methacholine required to produce a 20% fall in forced expiratory volume in one second (FEV1), is widely used as a diagnostic test for bronchial asthma as well as an index of asthma severity [1][2][3]. However, the use of BHR as an index of asthma severity has been questioned following prospective studies, that have shown poor correlation between PD20 and risks for clinical exacerbation [4][5][6] as well as in the detection of those at risk of fatal attacks [7][8][9].…”

mentioning

confidence: 99%

A new asthma severity index: a predictor of near-fatal asthma?

Lee¹,

Abisheganaden²,

Chee³

et al. 2001

Eur Respir J

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Bronchial hyperresponsiveness (BHR), measured as the provocative dose of inhaled histamine or methacholine required to produce a 20% fall in forced expiratory volume in one second (FEV1) (PD20), is widely used as one of the indices of asthma severity. Excessive bronchoconstriction, reflected by the maximal percentage fall in forced vital capacity (FVC) at PD20 (DFVC %) during BHR testing, is considered to be the most important pathophysiological determinant in fatal asthma. The present study hypothesized that an index which combines both the ease of airway narrowing and excessive bronchoconstriction, DFVC %/log(PD20), may be better in assessing asthma severity, especially in those at risk of near-fatal attacks.The dose-response curves of 46 asthmatics who underwent methacholine challenge testing were studied. Group 1 (n=14) patients had mild disease, Group 2 (n=21) had moderate disease and Group 3 (n=11) had severe disease, as classified according to the Global Initiative for Asthma. Nine patients had prior intubation for near-fatal asthma.DFVC %/log (PD20) was better than DFVC % and PD20 in categorizing patients into the three severity groups (pv0.0001), but more importantly, it was able to discriminate patients with previous intubation from those without (p=0.04). It also correlated better with FEV1 (% predicted), frequency of symptoms and inhaled steroid requirement than either index alone.It is concluded that the percentage fall in forced vital capacity/log of the provocative dose causing a 20% fall in forced expiratory volume in one second combines information on the ease and excessive degrees of airway narrowing in asthma. This new index may be better at assessing asthma severity and in discriminating those at risk of near-fatal attacks.

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Airway responsiveness to histamine as a test for overall severity of asthma in children

Cited by 110 publications

References 15 publications

PACAP Reverses Airway Hyperresponsiveness Induced by Ozone Exposure in Guinea Pigs

PACAP Reverses Airway Hyperresponsiveness Induced by Ozone Exposure in Guinea Pigs

Possible control of paternal imprinting of polymorphisms of the ADAM33 gene by epigenetic mechanisms and association with level of airway hyperresponsiveness in asthmatic children

A new asthma severity index: a predictor of near-fatal asthma?

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