Antonio Dellabianca

Toluene diisocyanate-induced asthma : clinical findings and bronchial responsiveness studies in 113 exposed subjects with work-related respiratory symptoms

We report the clinical findings and the results of inhalation challenge with toluene diisocyanate (TDI) and methacholine in 113 subjects with a history of exposure to TDI and work-related respiratory symptoms. Only some of the subjects (40.7%) had isocyanate asthma, diagnosed by a positive TDI inhalation challenge. Most reactors had a dual (30.4%) or a late (41.3%) response. The interval between the last occupational exposure and the specific challenge was significantly shorter in reactors, and among this group the number of immediate reactions to TDI decreased progressively with an increasing interval. The reactors had a significantly higher proportion of positive responses to methacholine and a significantly lower mean PD15 FEV-1 (provocative dose of methacholine which provoke a 15% decrease in forced expiratory volume in 1 second) (reactors: 557 micrograms, SEM 92.3; nonreactors: 1346 micrograms, SEM 128, P less than .01). Methacholine challenge could not identify subjects with isocyanate asthma.

Intestinal dysmotility and enteric neurochemical changes in a Parkinson's disease rat model

Gastrointestinal disorders, constipation in particular, are the most common non-motor dysfunctions affecting Parkinsons disease (PD) patients. We have previously reported that rats bearing unilateral nigrostriatal lesion caused by 6-hydroxydopamine (6-OHDA) stereotaxic injection develop severe constipation together with a region-specific decrease of neuronal nitric oxide synthase (nNOS) in enteric neurons of the lower intestinal tract. Here, we extend these observations on other enteric neuronal subpopulations, investigating also the propulsive activity of isolated colonic specimens. Four weeks post 6-OHDA injection, lesioned rats showed a significant increase of vasoactive intestinal polypeptide (VIP) concomitant with the reduced expression of nNOS in the myenteric plexus of distal ileum and proximal colon; in particular VIP increased in a subpopulation of neurons actively expressing nNOS. On the other hand, choline acetyltransferase (ChAT) was not modified in any of the intestinal segments analyzed. Interestingly, we found a reduced expression of dopamine receptor type 2 (D2R) in proximal (-66.8%) and distal (-54.5%) colon, together with reduced peristalsis efficiency (decrease in intraluminal pressure and frequency of peristaltic events) in the 6-OHDA-lesioned rats. The selective depletion of dopaminergic nigrostriatal neurons is associated with changes in the expression of enteric inhibitory neurotransmitters, as well as of the D2R in intestinal specific regions. Moreover, 6-OHDA-lesioned rats demonstrated altered colon propulsive activity referable to the D2R decrease. Our findings unveil subtle mechanisms underlying the enteric neurochemical plasticity events evoked by disruption of the normal brain-gut cross-talk, giving a peculiar point of view on the pathophysiology of the severe constipation that frequently affects PD patients.

Features and severity of occupational asthma upon diagnosis: an Italian multicentric case review

Background. The severity of occupational asthma (OA) at the time of diagnosis is not known. In this study we aimed to evaluate some features of the disease at the time of diagnosis, particularly looking at severity and treatment before diagnosis.

Irritant vocal cord dysfunction and occupational bronchial asthma: differential diagnosis in a health care worker

OBJECTIVES Vocal cord dysfunction (VCD) is an uncommon respiratory disease characterized by the paradoxical adduction of vocal cords during inspiration, that may mimic bronchial asthma. The pathogenesis of VCD has not been clearly defined but it is possible to recognize non-psychologic and psychologic causes. The majority of patients are female but, interestingly, a high incidence of VCD has been documented in health care workers. A misdiagnosis with asthma leads to hospitalisation, unnecessary use of systemic steroids with related adverse effects, and sometimes tracheostomy and intubation. In a subset of VCD patients, the disease can be attributed to occupational or environmental exposure to inhaled irritants. MATERIALS AND METHODS We report the case of a 45-year-old woman, working as a nurse, who complained of wheezing, cough, dyspnoea related to inhalation of irritating agents (isopropylic alcohol, formaldehyde, peracetic acid). She underwent chest radiography, pulmonary function assessment both in the presence and in the absence of symptoms, bronchial provocation with methacholine and bronchodilation test with salbutamol to recognize asthmas features, allergy evaluation by skin prick tests and patch tests and video-laryngoscopy. RESULTS VCD diagnosis was made on the basis of video-laryngoscopy, that visualized the paradoxical motion of the vocal cords during symptoms, in the absence of other pathologic processes. CONCLUSIONS This case fulfils the proposed criteria for the diagnosis of irritant VCD (IVCD). This is the first report of VCD onset following exposure to several irritants: formaldehyde, glutaraldehyde, sopropylic alcohol, peracetic acid-hydrogen peroxide mixture. These substances are used as cleaning and antiseptic agents in healthcare settings and some ones can also be found in many indoor environments. A correct diagnosis is important both to give the appropriate treatment and for medical legal implications.

Identification of galanin receptor 1 on excitatory motor neurons in the guinea pig ileum.

Abstract  Exogenously administered galanin inhibits cholinergic transmission to the longitudinal muscle and reduces peristaltic efficiency in the guinea pig ileum with a mechanism partially mediated by galanin receptor 1 (GAL‐R1). We investigated the effect of exogenous galanin 1–16, which has high affinity for GAL‐R1, on the ascending excitatory reflex of the circular muscle elicited by radial distension in isolated segments of guinea pig ileum. We used a three‐compartment bath that allows dissecting the ascending pathway into the oral (site of excitatory motor neurons), intermediate (site of ascending interneurons) and caudal compartment (site of intrinsic primary afferent neurons). Galanin 1–16 (0.3–3 μmol L−1) applied to the oral compartment inhibited in a concentration‐dependent manner the ascending excitatory reflex elicited by the wall distension in the caudal compartment. This effect was antagonized by the GAL‐R1 antagonist, RWJ‐57408 (1 and 10 μmol L−1). By contrast, galanin 1–16 was ineffective when added to the intermediate or caudal compartment up to 3 μmol L−1. GAL‐R1 immunoreactive neurons did not contain neuron‐specific nuclear protein, a marker for intrinsic primary afferent neurons. These findings indicate that GAL‐R1s are present on motor neurons responsible for the ascending excitatory reflex, but not on ascending interneurons and intrinsic primary afferent neurons.

Role of carbon monoxide in electrically induced non-adrenergic, non-cholinergic relaxations in the guinea-pig isolated whole trachea

Nitric oxide (NO) and vasoactive intestinal peptide (VIP) are considered transmitters of non‐adrenergic, non‐cholinergic (NANC) relaxations in guinea‐pig trachea, whereas the role of carbon monoxide (CO) is unknown. This study was designed to assess the participation of CO, and to investigate the localization of haem oxygenase‐2 (HO‐2), the CO‐producing enzyme, in tracheal neurons.

Adenosine A1 and A3 Receptor Agonists Inhibit Nonadrenergic, Noncholinergic Relaxations in the Guinea Pig Isolated Trachea

Background: Adenosine affects the tone and reactivity of airways by activating specific membrane receptors, named A₁, A_2a, A_2b and A₃. It affects cellular activities either directly by regulating membrane ion exchanges and polarization, or indirectly by modifying neurotransmitter release. Objectives: We assessed the effect of A₁ and A₃ receptor activation on electrically induced nonadrenergic, noncholinergic (NANC) relaxations in the guinea pig isolated trachea and the localization of A₁ and A₃ receptors in tracheal inhibitory neurons. Methods: NANC responses at 3 Hz were evaluat- ed in the presence of 2-chloro-N⁶-cyclopentyladenosine (CCPA), a selective A₁ agonist, and 2-chloro-N⁶-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Cl-IB-MECA), a selective A₃ agonist, before and after the administration of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A₁ antagonist, or 9-chloro-2-(2-furanyl)-5-((phenylacetyl)amino[1,2,4]triazolo[1,5-c])quinazoline (MRS 1220), a selective A₃ antagonist, respectively. For immunohistochemistry, tissues were exposed to antibodies to HuC/D, a general neuronal marker, neuronal nitric oxide synthase (nNOS), and A₁ or A₃ adenosine receptors and processed by indirect immunofluorescence. Results: CCPA (10 nM–3 μM) inhibited NANC relaxations. DPCPX (10 nM) failed to antagonize the effect of CCPA, but inhibited per se NANC relaxations (range 0.1–100 nM). CCPA (10 nM–10 μM) contracted unstimulated tracheal preparations, an effect antagonized by 10 nM DPCPX, with a pK_B value of 8.43. Cl-IB-MECA (10 nM–3 μM) inhibited NANC relaxations through a mechanism antagonized by MRS 1220 (100 nM). A₁- and A₃-positive neurons containing nNOS were detected in tracheal sections. Conclusions: Enogenous adenosine may induce airway hyperresponsiveness by inhibiting NANC relaxations via A₁ and A₃ receptors.

Inhaled ammonium persulphate inhibits non-adrenergic, non-cholinergic relaxations in the guinea pig isolated trachea.

Background: Persulphates can act both as irritants and sensitizers in inducing occupational asthma. A dysfunction of nervous control regulating the airway tone has been hypothesized as a mechanism underlying bronchoconstriction in asthma. Objectives: It was the aim of this study to investigate whether inhaled ammonium persulphate affects the non-adrenergic, non-cholinergic (NANC) inhibitory innervation, the cholinergic nerve-mediated contraction or the muscular response to the spasmogens, carbachol or histamine, in the guinea pig epithelium-free, isolated trachea. Methods: Male guinea pigs inhaled aerosols containing ammonium persulphate (10 mg/m3 for 30 min for 5 days during 3 weeks). Control animals inhaled saline aerosol. NANC relaxations to electrical field stimulation at 3 Hz were evaluated in whole tracheal segments as intraluminal pressure changes. Drugs inactivating peptide transmission, nitric oxide synthase, carbon monoxide production by haem oxygenase-2 and soluble guanylyl cyclase were used to assess the involvement of various inhibitory neurotransmitters. Carbachol and histamine cumulative concentration-response curves were obtained. Results: In both groups, nitric oxide and carbon monoxide participated to the same extent as inhibitory neurotransmitters. In exposed animals, the tracheal NANC relaxations were reduced to 45.9 ± 12.1% (p < 0.01). The cholinergic nerve-mediated contractions to electrical field stimulation and the muscular response to histamine were not modified by ammonium persulphate exposure. The muscular response to carbachol was unaffected up to 1 µM. Conversely, the response to the maximal concentration of carbachol (3 µM) was increased (p < 0.01). Conclusion: Ammonium persulphate inhalation at high concentrations impairs the nervous NANC inhibitory control in the guinea pig airways. This may represent a novel mechanism contributing to persulphate-induced asthma.