In mice of both sexes, repeated contractions of smooth muscle in vivo greatly enhance the response of peripheral airways to methacholine

Boucher, Magali; Dufour-Mailhot, Alexis; Tremblay-Pitre, Sophie; Khadangi, Fatemeh; Rojas‐Ruiz, Andrés; Henry, Cyndi; Bossé, Ynuk

doi:10.1016/j.resp.2022.103938

Cited by 6 publications

(27 citation statements)

References 71 publications

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“…In fact, the maximal changes in R rs5−19 , X rs5 , F res and Ax caused by methacholine were all at least 92% greater in the multiple‐ than the single‐concentration challenge in both the healthy and the asthmatic group (Table 2). In relation to ‘force adaptation’, these results suggest that its effect on respiratory mechanics has probably never been underestimated, since it has always been tested using oscillometry in the absence of DIs 9–11 …”

Section: Discussionmentioning

confidence: 96%

“…Evidently, this more than additive effect may also be attributed to 'force adaptation'. [5][6][7][8][9][10][11] Small airway narrowing is also inherently heterogeneous, [50][51][52][53] implying that more narrowing is expected to worsen narrowing heterogeneity and thus enhance the increase in R rs5À19 . In turn, a progressive increase in small airway narrowing heterogeneity also inevitably leads to a greater level of small airway closure (derecruitment).…”

Section: Discussionmentioning

confidence: 99%

“…In relation to 'force adaptation', these results suggest that its effect on respiratory mechanics has probably never been underestimated, since it has always been tested using oscillometry in the absence of DIs. [9][10][11] A greater increase in R rs5À19 indicates more narrowing of small airways 47 and/or more narrowing heterogeneity. 48 It is thus likely that, in the absence of DIs, there was a progressive narrowing of small airways.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11] This was demonstrated by showing that a methacholine challenge preceded by a period of 20-30 min of tone, induced by administering serial low concentrations of methacholine, leads to a greater final response than administering the same cumulative concentration in a single delivery. [9][10][11] Obviously, the final concentration used in these two challenges has always been significantly smaller in the challenge preceded by tone. The lack of cumulative effect of methacholine thus implies that the effect of 'force adaptation' on the in vivo response to methacholine has always been underestimated.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8] Although the effect of 'force adaptation' in vivo is difficult to investigate, many attempts suggested that it potentiates the response to methacholine. [9][10][11] This was demonstrated by showing that a methacholine challenge preceded by a period of 20-30 min of tone, induced by administering serial low concentrations of methacholine, leads to a greater final response than administering the same cumulative concentration in a single delivery. [9][10][11] Obviously, the final concentration used in these two challenges has always been significantly smaller in the challenge preceded by tone.…”

Section: Introductionmentioning

confidence: 99%

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The cumulative effect of methacholine on large and small airways when deep inspirations are avoided

et al. 2022

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Background and Objective: The effect of serial incremental concentrations of methacholine is only slightly cumulative when assessed by spirometry. This limited cumulative effect may be attributed to the bronchodilator effect of deep inspirations that are required between concentrations to measure lung function. Using oscillometry, the response to methacholine can be measured without deep inspirations. Conveniently, oscillometry can also dissociate the contribution of large versus small airways. Herein, oscillometry was used to assess the cumulative effect of methacholine in the absence of deep inspirations on large and small airways. Methods: Healthy and asthmatic volunteers underwent a multiple-concentration methacholine challenge on visit 1 and a single-concentration challenge on visit 2 using the highest concentration of visit 1. The maximal response was compared between visits to assess the cumulative effect of methacholine. The lung volume was also measured after the final concentration to assess hyperinflation. Results: In both healthy and asthmatic subjects, increases in resistance at 19 Hz (R rs19 ), reflecting large airway narrowing, did not differ between the multiple-and the single-concentration challenge. However, increases in resistance at 5 Hz (R rs5 ) minus R rs19 , reflecting small airway narrowing, were 117 and 270% greater in the multiplethan the single-concentration challenge in healthy (p = 0.006) and asthmatic (p < 0.0001) subjects, respectively. Hyperinflation occurred with both challenges and was greater in the multiple-than the single-concentration challenge in both groups. Conclusion: Without deep inspirations, the effect of methacholine is cumulative on small airways but not on large airways. Lung hyperinflation and derecruitment may partially explain these different responses.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The cumulative effect of methacholine on large and small airways when deep inspirations are avoided

et al. 2022

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Force adaptation through the intravenous route in naïve mice

Boucher

Henry

Bossé

2023

Experimental Lung Research

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Prenatal inflammation reprograms hyperactive ILC2s that promote allergic lung inflammation and airway dysfunction

López,

Griffin,

Aguilar

et al. 2023

Preprint

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Allergic asthma is a chronic respiratory disease that initiates in early life, but causal mechanisms are poorly understood. Here we examined how prenatal inflammation shapes allergic asthma susceptibility by reprogramming lung immunity from early development. Induction of Type I interferon-mediated inflammation during development provoked expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produced increased IL-5 and IL-13, and were associated with acute Th2 bias, eosinophilia, and decreased Tregs in the lung. The hyperactive ILC2 phenotype was recapitulated by adoptive transfer of a fetal liver precursor following exposure to prenatal inflammation, indicative of developmental programming. Programming of ILC2 function and subsequent lung immune remodeling by prenatal inflammation led to airway dysfunction at baseline and in response to papain, indicating increased asthma susceptibility. Our data provide a link by which developmental programming of progenitors by early-life inflammation drives lung immune remodeling and asthma susceptibility through hyperactivation of lung-resident ILC2s.One Sentence SummaryPrenatal inflammation programs asthma susceptibility by inducing the production of hyperactivated ILC2s in the developing lung.

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In mice of both sexes, repeated contractions of smooth muscle in vivo greatly enhance the response of peripheral airways to methacholine

Cited by 6 publications

References 71 publications

The cumulative effect of methacholine on large and small airways when deep inspirations are avoided

The cumulative effect of methacholine on large and small airways when deep inspirations are avoided

Force adaptation through the intravenous route in naïve mice

Prenatal inflammation reprograms hyperactive ILC2s that promote allergic lung inflammation and airway dysfunction

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