Airway narrowing and bronchodilation to deep inspiration in bronchial segments from subjects with and without reported asthma

Noble, Peter B.; Jones, Robyn L.; Cairncross, Alvenia; Elliot, John; Mitchell, Howard; McFawn, Peter K.

doi:10.1152/japplphysiol.01489.2012

Cited by 57 publications

(49 citation statements)

References 53 publications

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“…Recent studies of intact airways now cast substantial doubt and confusion as to how or even if the sensitivity of ASM force generation to imposed realistic Ptm oscillations are relevant to explain reactivity at the whole airway level (31,32,43,44,46). In this study, we extended the results of LaPrad et al (31,32) and Noble et al (43,44,46) by examining Ptm oscillations from FRC, as is typically imposed in situ. We used an integrated system with real-time ultrasound imaging to quantify the effect of small and large Ptm oscillations from a Ptm corresponding to either a normal or a reduced FRC on the reactivity and mechanical properties of an intact airway.…”

Section: Discussionmentioning

confidence: 88%

“…In this study, we attempt to explicitly establish how behavior from isolated ASM strip studies translates to the whole airway. Recently, several groups have examined the impact of fluctuating stress and strain applied to isolated airways (31,32,43,44,46) or airways residing in lung slices (34). LaPrad et al (31) showed in intact bovine airways that transmural pressure (Ptm) fluctuations associated with tidal breaths and DIs imposed around a constant mean Ptm of 5 cmH 2 O were relatively ineffective at reversing narrowing.…”

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confidence: 99%

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Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation?

Harvey

Parameswaran

Lutchen

2013

Journal of Applied Physiology

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Harvey BC, Parameswaran H, Lutchen KR. Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation?. J Appl Physiol 115: 436 -445, 2013. First published May 30, 2013 doi:10.1152/japplphysiol.00009.2013.-Fluctuating forces imposed on the airway smooth muscle due to breathing are believed to regulate hyperresponsiveness in vivo. However, recent animal and human isolated airway studies have shown that typical breathing-sized transmural pressure (Ptm) oscillations around a fixed mean are ineffective at mitigating airway constriction. To help understand this discrepancy, we hypothesized that Ptm oscillations capable of producing the same degree of bronchodilation as observed in airway smooth muscle strip studies requires imposition of strains larger than those expected to occur in vivo. First, we applied increasingly larger amplitude Ptm oscillations to a statically constricted airway from a Ptm simulating normal functional residual capacity of 5 cmH2O. Tidal-like oscillations (5-10 cmH2O) imposed 4.9 Ϯ 2.0% strain and resulted in 11.6 Ϯ 4.8% recovery, while Ptm oscillations simulating a deep inspiration at every breath (5-30 cmH2O) achieved 62.9 Ϯ 12.1% recovery. These same Ptm oscillations were then applied starting from a Ptm ϭ 1 cmH2O, resulting in approximately double the strain for each oscillation amplitude. When extreme strains were imposed, we observed full recovery. On combining the two data sets, we found a linear relationship between strain and resultant recovery. Finally, we compared the impact of Ptm oscillations before and after constriction to Ptm oscillations applied only after constriction and found that both loading conditions had a similar effect on narrowing. We conclude that, while sufficiently large strains applied to the airway wall are capable of producing substantial bronchodilation, the Ptm oscillations necessary to achieve those strains are not expected to occur in vivo.airway smooth muscle; intact airways; bronchodilation; bronchoprotection; asthma WHEN PERIODIC LENGTH OSCILLATIONS mimicking tidal breathing and deep inspirations (DIs) are applied to airway smooth muscle (ASM) during or after excitation, the increase in ASM force is less than would otherwise have occurred, if the excitatory stimulus were applied while the ASM was static (13,21,61). This observation led to the notion that periodic length fluctuations perturb the binding of myosin to actin (14,33,38,48), or cause remodeling of the contractile apparatus (19,30,50), thereby limiting the resultant tension that the ASM can generate. With regard to asthma, the isolated ASM studies motivated the conjecture that the mechanism behind the beneficial effect of DIs in preventing airway hyperresponsiveness (AHR) is intricately tied to stretching of the ASM during breathing (13,17,29,48). By extrapolation, these ASM strip level studies led to the hypothesis that, in asthmatic subjects, conditions such as wall remodeling or the presence of a milieu of inflammatory mediators could all...

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Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation?

Harvey

Parameswaran

Lutchen

2013

Journal of Applied Physiology

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“…Because the remodeling in the airway wall may have changed the quantity of ASM relative to that of the connective tissues and epithelium, the results on reactivity may have been misinterpreted (13). Wholeairway comparisons in MCh dose-response between control subjects and subjects with asthma have also been done recently, and showed a clear decrease in airway diameter at every dose in subjects with asthma, but no changes in sensitivity of the airways to MCh (14). However, it is unknown to what extent those dose-responses were affected by the epithelium and other airway wall tissues.…”

Section: Discussionmentioning

confidence: 99%

Human Trachealis and Main Bronchi Smooth Muscle Are Normoresponsive in Asthma

Ijpma

Kachmar

Matusovsky

et al. 2015

Am J Respir Crit Care Med

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Rationale: Airway smooth muscle (ASM) plays a key role in airway hyperresponsiveness (AHR) but it is unclear whether its contractility is intrinsically changed in asthma.Objectives: To investigate whether key parameters of ASM contractility are altered in subjects with asthma.Methods: Human trachea and main bronchi were dissected free of epithelium and connective tissues and suspended in a force-length measurement set-up. After equilibration each tissue underwent a series of protocols to assess its methacholine dose-response relationship, shortening velocity, and response to length oscillations equivalent to tidal breathing and deep inspirations.Measurements and Main Results: Main bronchi and tracheal ASM were significantly hyposensitive in subjects with asthma compared with control subjects. Trachea and main bronchi did not show significant differences in reactivity to methacholine and unloaded tissue shortening velocity (Vmax) compared with control subjects. There were no significant differences in responses to deep inspiration, with or without superimposed tidal breathing oscillations. No significant correlations were found between age, body mass index, or sex and sensitivity, reactivity, or Vmax.Conclusions: Our data show that, in contrast to some animal models of AHR, human tracheal and main bronchial smooth muscle contractility is not increased in asthma. Specifically, our results indicate that it is highly unlikely that ASM half-maximum effective concentration (EC 50 ) or Vmax contribute to AHR in asthma, but, because of high variability, we cannot conclude whether or not asthmatic ASM is hyperreactive.

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“…tidal breathing and DI manoeuvres) 21,25,26 (Supplementary Figure S1). 21 To assess whether any changes in airway narrowing observed with TNF and IL-1β were as a result of increased ASM force, in a separate group of airways, DRCs were constructed to ACh under isovolumic conditions to measure active lumen pressure (proportional to ASM tension).…”

Section: Organ Bath and Syringe Pumpmentioning

confidence: 99%

TNF and IL‐1β exposure increases airway narrowing but does not alter the bronchodilatory response to deep inspiration in airway segments

et al. 2016

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Background and objective: While chronic inflammation of the airway wall and the failure of deep inspiration (DI) to produce bronchodilation are both common to asthma, whether pro-inflammatory cytokines modulate the airway smooth muscle response to strain during DI is unknown. The primary aim of the study was to determine how an inflammatory environment (simulated by the use of pro-inflammatory cytokines) alters the bronchodilatory response to DI. Methods: We used whole porcine bronchial segments in vitro that were cultured in medium containing tumour necrosis factor and interleukin-1β for 2 days. A custom-built servo-controlled syringe pump and pressure transducer was used to measure airway narrowing and to simulate tidal breathing with intermittent DI manoeuvres. Results: Culture with tumour necrosis factor and interleukin-1β increased airway narrowing to acetylcholine but did not affect the bronchodilatory response to DI. Conclusion: The failure of DI to produce bronchodilation in patients with asthma may not necessarily involve a direct effect of pro-inflammatory cytokines on airway tissue. A relationship between inflammation and airway hyper-responsiveness is supported, however, regulated by separate disease processes than those which attenuate or abolish the bronchodilatory response to DI in patients with asthma.

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Airway narrowing and bronchodilation to deep inspiration in bronchial segments from subjects with and without reported asthma

Cited by 57 publications

References 53 publications

Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation?

Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation?

Human Trachealis and Main Bronchi Smooth Muscle Are Normoresponsive in Asthma

TNF and IL‐1β exposure increases airway narrowing but does not alter the bronchodilatory response to deep inspiration in airway segments

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