Isolated Bronchi of Patients with COPD Show Decreased Histamine Responsiveness Compared to Smokers with Normal Lung Function

Abstract

This study compared airway responsiveness in vitro, as measured in isolated bronchi, with responsiveness in vivo in patients with COPD and smokers with normal lung function. In 9 patients with COPD (mean (range) FEV, 55 (30-78) %predicted) and 8 smokers with normal lung function (FEV1 101 (89-117) %predicted), who underwent surgery for lung cancer, responses to inhaled histamine and salbutamol were assessed before surgery. Bronchial specimens of 1-4 mm internal diameter were studied in the organ bath and histamine concentration-response curves assessed. All patients with COPD and none of the control individuals were hyperresponsive to inhaled histamine. Five patients with COPD and no control patient showed a bronchodilator response to salbutamol. Opposite to these findings, bronchial rings in the organ bath demonstrated a rightward shift of histamine concentration-response curves in COPD compared to controls, (p < 0.005). Accordingly, pED50 but not Emax differed statistically (p = 0.0016) between groups, mean+/-SEM values of pED50 in COPD (controls) being 4.67+/-0.08 (5.29+/-0.15) and of Emax 672+/-86 (772+/-120) mg. Patients with COPD showing hyperresponsiveness to inhaled histamine demonstrated lower responsiveness of their isolated bronchi compared to smokers with normal lung function. This suggests that in vivo hyperresponsiveness is based on other mechanisms than alterations in smooth muscle physiology.

The relationship between inspiratory lung function parameters and airway hyper-responsiveness in subjects with mild to moderate COPD

“…In a study by Kanner et al, the prevalence of BHR in subjects with mild COPD varied between 25-48%; furthermore, the prevalence of BHR was reported to be approximately 66% in mild or early COPD subjects in the Lung Health Study [21,22]. However, a study by Taube et al of nine subjects with stable, mild to severe COPD found a positive challenge test for all nine subjects after administering inhaled histamine [23]. Asthma patients were excluded from our study.…”

Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders

“…Of note, while subsegmental bronchi provide the greatest airway resistance along the bronchial tree, the contribution of bronchioles to airway resistance is very limited (Brooks, 1995;Thien, 2013). Indeed, the ASM tone detectable in medium isolated bronchi is related to the change in forced expiratory volume in 1 s (FEV 1 ) (Brown et al, 2006;Rogliani et al, 2015;Rogliani, Ritondo, Facciolo, et al, 2021b;Taube et al, 2006). On the other hand, the luminal area of small isolated airways is related to the forced expiratory flow between 25% and 75% of vital capacity (FEF 25-75 ), that is a predictive marker of peripheral obstruction leading to small airway disease (SAD) in the so-called 'silent zone' (Hogg et al, 2013;Kwon et al, 2020;Martin et al, 2013;Rogliani et al, 2015Rogliani et al, , 2023Usmani et al, 2021) (Figure 3a,b).…”

Airway hyperresponsiveness and chronic obstructive pulmonary disease outcomes

“…This is supported by the observation that resected airway smooth muscle from patients with COPD with in vivo direct AHR does not demonstrate ex vivo AHR. 5 Direct AHR in patients with COPD is also significantly associated with gas trapping/hyperinflation. 6 Patients with COPD who also have asthma (some would call this ''COPD and asthma,'' and others would use the term ''asthma-COPD overlap syndrome'' or ACOS) will also manifest asthmatic AHR, including indirect AHR.…”