Value of lung diffusing capacity for nitric oxide in systemic sclerosis.

A decreased lung diffusing capacity for carbon monoxide (DL ) in systemic sclerosis (SSc) is considered to reflect losses of alveolar membrane diffusive conductance for CO (DM ), due to interstitial lung disease, and/or pulmonary capillary blood volume (V ), due to vasculopathy. However, standard DL does not allow separate DM from V . Lung diffusing capacity for nitric oxide (DL ) is considered to be more sensitive to decrement of alveolar membrane diffusive conductance than DL .

Interactions between glycopyrronium and indacaterol on cholinergic neurotransmission and contractile response in bovine trachealis.

Background: Muscarinic-receptor antagonists and β-adrenoceptor agonists are used, alone or in combination, as first-line treatment for chronic obstructive pulmonary disease. Both drugs decrease airway smooth muscle tone by post-junctional mechanisms but they may have opposing effects on pre-junctional acetylcholine (ACh)-release.

Methods: We studied the effects of the muscarinic-receptor antagonist glycopyrronium (GLY), the β-adrenoceptor agonist indacaterol (IND) and their combination on electrically-induced ACh-release and contractile response in isolated bovine trachealis.

Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias.

Lung diffusing capacity for carbon monoxide (DLCO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DLCO to changes in alveolar membrane diffusive conductance (DMCO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DLNO) better reflects fibrotic changes than DLCO DLNO-DLCO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP.

Severity grading of chronic obstructive pulmonary disease: the confounding effect of phenotype and thoracic gas compression.

Current guidelines recommend severity of chronic obstructive pulmonary disease be graded by using forced expiratory volume in 1 s (FEV1). But this measurement is biased by thoracic gas compression depending on lung volume and airflow resistance. The aim of this study was to test the hypothesis that the effect of thoracic gas compression on FEV1 is greater in emphysema than chronic bronchitis because of larger lung volumes, and this influences severity classification and prognosis.

Gz- and not Gi-proteins are coupled to pre-junctional μ-opioid receptors in bovine airways.

We investigated the signal transmission pathway by which activation of μ-opioid receptors attenuates acetylcholine (ACh) release in bovine trachealis. Electrical stimulation (ES)-induced [(3)H]-ACh release was determined in bovine tracheal smooth muscle strips pre-incubated with either the Gi-protein inhibitor pertussis toxin (PTX, 500 ng/ml and 1 μg/ml) or the Gz-protein specific inhibitor arachidonic acid (AA, 10(-6)M and 10(-5)M) and then treated with DAMGO (D-Ala(2),N-MePhe(4),Gly-ol(5)-enkephalin) 10(-5)M. Indomethacin 10(-5)M was used to block AA cascade.

Assessment of extravascular lung water by quantitative ultrasound and CT in isolated bovine lung.

Lung ultrasonography (LUS) and computed tomography (CT) were compared for quantitative assessment of extravascular lung water (EVLW) in 10 isolated bovine lung lobes. LUS and CT were obtained at different inflation pressures before and after instillation with known amounts of hypotonic saline. A video-based quantitative LUS analysis was superior to both single-frame quantitative analysis and visual scoring in the assessment of EVLW.

Effects of κ- and μ-opioid agonists on cholinergic neurotransmission and contraction in isolated bovine trachealis.

The effects of the selective μ-opioid agonist DAMGO and the selective κ-opioid agonist U-50488H on tritiated acetylcholine release ([(3)H]-ACh) and contractile responses to electrical stimulation (ES) were simultaneously determined in isolated bovine trachealis. The inhibitory effect of DAMGO 10(-5)M on [(3)H]-ACh release was not significantly different from the effect of the non-selective muscarinic agonist pilocarpine 10(-5)M, whereas the effect of U-50488H 10(-5)M was significantly greater. The effects of both opioids were not significantly different when muscles were pre- or co-incubated with the unselective muscarinic antagonist atropine 10(-7)M.

Pre-junctional muscarinic autoreceptors in bovine airways.

Unlabelled: We searched for pre-junctional inhibitory muscarinic receptors in isolated bovine trachealis strips and bronchial rings. Electric stimulation (ES)-induced tritiated acetylcholine ([(3)H]-ACh)-release and isometric contractions were determined in muscles incubated with the non-selective muscarinic agonist pilocarpine, the non-selective muscarinic antagonist atropine, the selective M(2)-receptor antagonists methoctramine and gallamine, or the selective M(4)-receptor antagonist PD102807. Electric field stimulation (EFS)-induced isometric contractile responses were assessed in trachealis strips and bronchial rings treated with 10(-9)-10(-5)M methoctramine, gallamine or PD102807.

Formoterol by pressurized metered-dose aerosol or dry powder on airway obstruction and lung hyperinflation in partially reversible COPD.

Background: We compared the efficacy and safety of formoterol given by a pressurized metered-dose inhaler (pMDI) (Atimos®, Chiesi Farmaceutici, Italy), using a chlorine-free hydrofluoroalkane (HFA-134a) propellant developed to provide stable and uniform dose delivery (Modulite™, Chiesi Farmaceutici, Italy), with formoterol by dry powder inhaler (DPI) (Foradil® Aerolizer®, Novartis Pharmaceuticals) and placebo, in reducing airflow obstruction and lung hyperinflation, in moderate-to-severe, partially reversible chronic obstructive pulmonary disease (COPD).

Methods: Forty-eight patients were randomized to a 1-week, double-blind, double-dummy, three-period crossover study with 12 μg b.i.

Does a low-density gas mixture or oxygen supplementation improve exercise training in COPD?

Background: Low-density gas mixtures and oxygen (O₂) supplementation are known to improve physical performance and ventilatory adaptation during incremental maximal exercise in COPD. We investigated whether their combined use during intense physical training is also effective in ameliorating exercise tolerance in patients affected by moderate to severe COPD.

Methods: Thirty patients (FEV₁ < 60% of predicted) underwent a 2-month rehabilitation program.

Beta-Adrenergic Agonists.

Inhaled β₂-adrenoceptor (β₂-AR) agonists are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptoms-relievers and, in combination with inhaled corticosteroids, as disease-controllers. In this article, we first review the basic mechanisms by which the β₂-adrenergic system contributes to the control of airway smooth muscle tone. Then, we go on describing the structural characteristics of β₂-AR and the molecular basis of G-protein-coupled receptor signaling and mechanisms of its desensitization/ dysfunction.

Noninflammatory mechanisms of airway hyper-responsiveness in bronchial asthma: an overview.

Airway hyper-responsiveness (AHR) is a cardinal feature of asthma. Its absence has been considered useful in excluding asthma, whereas it may be present in other diseases such as atopic rhinitis and chronic obstructive pulmonary disease. AHR is often considered an epiphenomenon of airway inflammation.

Bronchodilator effects of exercise hyperpnea and albuterol in mild-to-moderate asthma.

In asthmatic patients, either bronchodilatation or bronchoconstriction may develop during exercise. In 18 patients with mild-to-moderate asthma, we conducted two studies with the aims to 1) quantify the bronchodilator effect of hyperpnea induced by incremental-load maximum exercise compared with effects of inhaled albuterol (study 1, n=10) and 2) determine the time course of changes in airway caliber during prolonged constant-load exercise (study 2, n=8). In both studies, it was also investigated whether the bronchodilator effects of exercise hyperpnea and albuterol are additive.

Airway smooth muscle as a model for new investigative drugs in asthma.

Bronchial asthma as such exists because airway smooth muscle (ASM) contracts excessively in response to various stimuli. After several decades during which research was mainly focused on airway inflammation, increasing attention is now being paid to a possible abnormal behaviour of ASM. Thus, ASM is regarded as a major target for anti-asthma treatments.

Environmental dust granulometry and microbial load in the presence of tobacco smoke.

Background And Objective: Several studies describe damage from passive smoking in humans. However, it is not clearly understood how different chemical and physical components relate to mechanisms of damage. This investigation was focused on the particulate phase of environmental cigarette smoke.

Airway responsiveness to methacholine and deep inhalations in subjects with rhinitis without asthma.

Background: Airway hyperresponsiveness in asthma is believed to be caused in part by the inability of deep inspirations to modulate airway narrowing.

Objective: We investigated whether deep inspirations taken before or after methacholine inhalation attenuate bronchoconstriction in subjects with rhinitis. The results were compared with a group of healthy subjects.

Atopy in wheezing infants always starts with monosensitization.

Previously, evidence has been provided that sensitization is frequent in asthmatic children and polysensitization represents the natural history of allergy. The aim of this study was to investigate whether polysensitization may occur primarily in infants with wheezing. Thus, 98 infants (<1 year of age) were studied at the onset of wheezing symptoms.

Cysteinyl-leukotrienes in the regulation of beta2-adrenoceptor function: an in vitro model of asthma.

Background: The response to beta2-adrenoceptor agonists is reduced in asthmatic airways. This desensitization may be in part due to inflammatory mediators and may involve cysteinyl-leukotrienes (cysteinyl-LTs). Cysteinyl-LTs are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions.

Allergic airway inflammation and beta-adrenoceptor dysfunction.

A reduced response to beta-adrenoceptor agonists has been reported in airways of asthmatic subjects. Mechanisms for beta-adrenoceptor dysfunction are (1) inactivation or downregulation of beta-adrenoceptors by specific agonists (homologous desensitization) or by inflammatory mediations (heterologous desensitization), (2) inactivation or downregulation of second messengers of beta-adrenoceptor pathway. Studies from our laboratory have shown that allergen challenge of passively sensitized human bronchi causes a beta-adrenoceptor dysfunction as a result of reduced activity of the receptor-coupled Gs protein.

A model of allergen-driven human airway contraction: beta2 pathway dysfunction without cytokine involvement.

Background: In our previous in vitro model, allergen incubation of passively sensitized human airways reduced the response to salbutamol. However, whether cytokines play a role in this model is still unknown.

Objective: To investigate interleukin 1beta and tumor necrosis factor a expression in allergen-challenged human airways.