Heterogeneity of airway hyperresponsiveness

CROWTHER, S. D.; CHAPMAN, I. D.; MORLEY, J.

doi:10.1046/j.1365-2222.1997.d01-561.x

Cited by 5 publications

(7 citation statements)

References 58 publications

(97 reference statements)

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“…Similarly, single spasmogen studies have failed to reveal airway hyperresponsiveness to iv histamine at any time up to 72 hr after ovalbumin challenge (Banner et al 1996) or to acetylcholine (Heuer et al 1994). We have found only one other study which examined a wide range of spasmogens (Crowther et al 1997). In common with our results, these authors also claimed that antigen induced a hyperresponsiveness that was said to be heterogeneous.…”

Section: Discussionsupporting

confidence: 62%

“…With no more than two spasmogens under study, however, it is difficult to assess to what extent the airway hyperresponsiveness is non-specific. Similarly, the hyperresponsiveness in anaesthetised guinea-pigs measured immediately after an infusion of the antigen has been described as heterogeneous since there was a variable degree of increased reactivity to a wider range of intravenously administered spasmogens (Crowther et al 1997). The aim of the present study was therefore to investigate whether an aerosolised antigen-challenge leads to airway hyperresponsiveness (measured 18 to 24 hr after challenge) to a wide variety of intravenously administered spasmogens in sensitised, anaesthetised guinea-pigs.…”

mentioning

confidence: 99%

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Airway Hyperresponsiveness in Anaesthetised Guinea‐Pigs 18–24 Hours after Antigen Inhalation Does Not Occur with All Intravenously Administered Spasmogens

Johnson

Broadley

1999

Pharmacology & Toxicology

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Actively sensitised guinea-pigs were exposed to inhalation challenges with ovalbumin aerosol (macro-and microshock) and airway responsiveness to six intravenously administered spasmogens was evaluated 18 to 24 hr later in the anaesthetised animal. An increase in airway sensitivity was defined as a significant leftward shift of the dose-response curve when compared with saline-challenged control sensitized animals. After ovalbumin-macroshock (I% ovalbumin for 2 min. with mepyramine cover against fatal anaphylaxis), airway hyperresponsiveness was seen to 5-HT, the thromboxane A2-mimetic, U-46619, and bradykinin but not to methacholine, histamine or substance I? A similar pattern was seen after ovalbumin-microshock (0.01% ovalbumin for 60 min.). with induction of airway hyperreactivity to 5-HT and U-46619 but not methacholine or histamine. When the U-46619 dose-response curve was constructed following treatment of the animals with atropine (1 mgikg. intravenously), airway hyperresponsiveness was no longer significant. As an index of airway inflammation, lung weights were significantly heavier in ovalbumin-challenged animals, than in saline-challenged controls. The results of this study with intravenously administered spasmogens does not support claims that ovalbumininduced airway hyperreactivity in the guinea-pig is a 'non-specific' phenomenon.

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Section: Discussionsupporting

confidence: 62%

mentioning

confidence: 99%

Airway Hyperresponsiveness in Anaesthetised Guinea‐Pigs 18–24 Hours after Antigen Inhalation Does Not Occur with All Intravenously Administered Spasmogens

Johnson

Broadley

1999

Pharmacology & Toxicology

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“…The heterogeneity of airway hyperresponsiveness has been clearly defined [25] and airway hyperresponsiveness is more complex than was once thought. Even methacholine and histamine, which are both directly reactive to smooth muscle, show differences in airway responsiveness.…”

Section: Discussionmentioning

confidence: 99%

Severity of exercise-induced bronchoconstriction is related to airway eosinophilic inflammation in patients with asthma

Yoshikawa

Shoji²,

Fujii³

et al. 1998

Eur Respir J

125

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Exercise-induced bronchoconstriction (EIB) is widely prevalent in asthmatic patients. Eosinophilic airway inflammation is considered to be a major factor in the pathogenesis of asthma. However, the effects of eosinophilic airway inflammation on EIB have been elucidated insufficiently. To examine the relationship between the severity of EIB and eosinophilic inflammation, sputum induction and exercise challenge were performed in 21 asthmatic patients. Significantly higher percentages of eosinophils and levels of eosinophil cationic protein (ECP) were found in induced sputum in EIB-positive asthmatics (median (range), eosinophils: 23.5 (11.0-61.0)%; ECP: 1,475 (74.8-17,701) ng x mL(-1)) than in EIB-negative asthmatics (eosinophils: 6.0 (1.0-41.5)% (p=0.006); ECP: 270.6 (10.8-7,700) ng x mL(-1) (p=0.049)). There was a significant correlation between the severity of EIB and the sputum eosinophil percentage (r=0.59, p=0.009) and the level of ECP (r=0.47, p=0.037). The area under the curve of the forced expiratory volume in one second for 30 min after exercise correlated with the percentage of eosinophils (r=0.60, p=0.008) and the level of ECP (r=0.45, p=0.04). There was no correlation between airway responsiveness to methacholine on the one hand and EIB, sputum eosinophils or ECP on the other. In conclusion, these results provide evidence that the severity of bronchoconstriction evoked by exercise is more closely related to eosinophilic airway inflammation than airway hyperresponsiveness to methacholine in asthmatic patients.

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“…Innate biological variability of airway responsiveness across airways even within the same animal is quite large and does not follow a normal distribution (2,3,23). For example, Minshall and colleagues showed at the level of human lung slices that airway responses are remarkably heterogeneous Figure 3.…”

Section: Discussionmentioning

confidence: 99%

“…Assessment in the living animal offers the advantage of studying the airway in its native microenvironment (1), but because responses of individual airways are innately and dramatically heterogeneous (2)(3)(4)(5), inference of airway behavior is indirect, complex, and often ambiguous (6,7) and is costly in terms of time and money. The ASM strip (8)(9)(10) or ASM cell (4, 11-13) isolated from trachea or major bronchi provides a direct and unambiguous assessment of muscle contractility, but results so obtained may not be representative of responses of muscle from smaller airways.…”

Section: Clinical Relevancementioning

confidence: 99%

Airway Contractility in the Precision-Cut Lung Slice after Cryopreservation

Rosner¹,

Ram-Mohan

Paez-Cortez

et al. 2014

Am J Respir Cell Mol Biol

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An emerging tool in airway biology is the precision-cut lung slice (PCLS). Adoption of the PCLS as a model for assessing airway reactivity has been hampered by the limited time window within which tissues remain viable. Here we demonstrate that the PCLS can be frozen, stored long-term, and then thawed for later experimental use. Compared with the never-frozen murine PCLS, the frozenthawed PCLS shows metabolic activity that is decreased to an extent comparable to that observed in other cryopreserved tissues but shows no differences in cell viability or in airway caliber responses to the contractile agonist methacholine or the relaxing agonist chloroquine. These results indicate that freezing and long-term storage is a feasible solution to the problem of limited viability of the PCLS in culture.

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Heterogeneity of airway hyperresponsiveness

Cited by 5 publications

References 58 publications

Airway Hyperresponsiveness in Anaesthetised Guinea‐Pigs 18–24 Hours after Antigen Inhalation Does Not Occur with All Intravenously Administered Spasmogens

Airway Hyperresponsiveness in Anaesthetised Guinea‐Pigs 18–24 Hours after Antigen Inhalation Does Not Occur with All Intravenously Administered Spasmogens

Severity of exercise-induced bronchoconstriction is related to airway eosinophilic inflammation in patients with asthma

Airway Contractility in the Precision-Cut Lung Slice after Cryopreservation

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