Differential association of MUC5AC and CLCA1 expression in small cartilaginous airways of RAO-affected and control horses

REASONS FOR PERFORMING STUDY: Airway mucus accumulation is associated with indoor irritant and allergen exposure in horses with recurrent airway obstruction (RAO). Epidermal growth factor receptor (EGFR) and a chloride channel (calcium activated, family member 1; CLCA1) are key signalling molecules involved in mucin gene expression. OBJECTIVES: We hypothesised that exposure to irritants and aeroallergens would lead to increased expression of the mucin gene eqMUC5AC and increased stored mucosubstance in the airways of RAO-affected horses, associated with increased neutrophils and CLCA1 and EGFR mRNA levels. METHODS: We performed quantitative RT-PCR of eqMUC5AC, CLCA1 and EGFR; volume density measurements of intraepithelial mucosubstances; and cytological differentiation of intraluminal inflammatory cells in small cartilaginous airways from cranial left and right and caudal left and right lung lobes of 5 clinically healthy and 5 RAO-affected horses that had been exposed to indoor stable environment for 5 days before euthanasia. RESULTS: Neutrophils were increased in RAO-affected horses compared to clinically healthy controls. EqMUC5AC mRNA levels were positively correlated with both CLCA1 and EGFR mRNA levels in RAO-affected horses but only with CLCA1 in controls. The relationship between eqMUC5AC and CLCA1 differed in the 2 groups of horses with RAO-affected animals overexpressing CLCA1 in relation to eqMUC5AC. CONCLUSIONS: These data implicate CLCA1 as a signalling molecule in the expression of eqMUC5AC in horses but also suggest differential regulation by CLCA1 and EGFR between horses with RAO and those with milder degrees of airway inflammation.

Anesthetic and Airways Management of a Dog with Severe Tracheal Collapse during Intraluminal Stent Placement

This case report describes the anesthetic and airways management of a dog affected by 4th degree tracheal collapse and undergoing endoscope-guided intraluminal stent placement. After premedication with acepromazine and butorphanol, general anesthesia was induced with propofol and maintained with intravenous propofol and butorphanol in constant rate infusion. During intraluminal stent placement, oxygen was supplemented by means of a simple and inexpensive handmade device, namely, a ureteral catheter inserted into the trachea and connected to an oxygen source, which allowed for the maintenance of airways’ patency and adequate patient’s oxygenation, without decreasing visibility in the surgical field or interfering with the procedure. The use of the technique described in the present paper was the main determinant of the successful anesthetic management and may be proposed for similar critical cases in which surgical manipulation of the tracheal lumen, which may potentially result in hypoxia by compromising airways patency, is required.

Abnormal small airways function in children with mild asthma

BACKGROUND Small airways disease is a hallmark in adults with persistent asthma, but little is known about small airways function in children with mild asthma and normal spirometry. We assessed ventilation heterogeneity, a marker of small airways function, with an easy tidal breath single-breath washout (SBW) technique in school-aged children with mild asthma and normal FEV1 and healthy age-matched control subjects. METHODS The primary outcome was the double-tracer gas phase III slope (SDTG), an index of ventilation heterogeneity in acinar airways derived from the tidal double-tracer gas SBW test. The second outcome was the nitrogen phase III slope (SN2), an index of global ventilation heterogeneity derived from the tidal nitrogen SBW test using pure oxygen. Triplicate SBW and spirometry tests were performed in healthy children (n = 35) and children with asthma (n = 31) at baseline and in children with asthma after bronchodilation. RESULTS Acinar (SDTG) but not global (SN2) ventilation heterogeneity was significantly increased in asthma despite normal FEV1. Of the 31 children with asthma, abnormal results were found for SDTG (≤ -2 z scores) in 11; forced expiratory flow, midexpiratory phase (FEF25%-75%) in three; and FEV1 in zero. After bronchodilation, SDTG, SN2, FEF25%-75%, and FEV1 significantly changed (mean [95% CI] change from baseline, 36% [15%-56%], 38% [18%-58%], 17% [9-25%], and 6% [3%-9%], respectively). CONCLUSIONS Abnormal acinar ventilation heterogeneity in one-third of the children suggests that small airways disease may be present despite rare and mild asthma symptoms and normal spirometry. The easy tidal SBW technique has considerable potential as a clinical and research outcome in children with asthma.

Working along sudden gains: Responsiveness on small and subtle early changes and exceptions

When mental health is monitored over the course of treatment, many clients report strong and stable changes, particularly early in psychotherapy. Such changes can occur both in singular events, such as sudden gains in particular symptoms, and more comprehensive ways across the World Health Organization definition of health (WHO, 1948), which includes well-being and psychosocial functioning. The present practical guideline illustrates a systematized sequence of tasks that explore rapid changes and sudden gains at a very early stage of therapy, as well as how such changes can be used in future therapeutic work. These tasks include (1) exploration of the change situation, (2) reinforcement of generalized self-efficacy and hope bonding, and (3) benefit for therapy.

Current concepts: host-pathogen interactions in cystic fibrosis airways disease.

Chronic infection and inflammation are defining characteristics of cystic fibrosis (CF) airway disease. Conditions within the airways of patients living with CF are conducive to colonisation by a variety of opportunistic bacterial, viral and fungal pathogens. Improved molecular identification of microorganisms has begun to emphasise the polymicrobial nature of infections in the CF airway microenvironment. Changes to CF airway physiology through loss of cystic fibrosis transmembrane conductance regulator functionality result in a wide range of immune dysfunctions, which permit pathogen colonisation and persistence. This review will summarise the current understanding of how CF pathogens infect, interact with and evade the CF host.

The bilateral responsiveness between intestinal microbes and IgA

The immune system has developed strategies to maintain a homeostatic relationship with the resident microbiota. IgA is central in holding this relationship, as the most dominant immunoglobulin isotype at the mucosal surface of the intestine. Recent studies report a role for IgA in shaping the composition of the intestinal microbiota and exploit strategies to characterise IgA-binding bacteria for their inflammatory potential. We review these findings here, and place them in context of the current understanding of the range of microorganisms that contribute to the IgA repertoire and the pathways that determine the quality of the IgA response. We examine why only certain intestinal microbes are coated with IgA, and discuss how understanding the determinants of this specific responsiveness may provide insight into diseases associated with dysbiosis.

Multifaceted responsiveness

The idea of responsiveness is closely related to therapist style and therapeutic relationship. While this may be the most important aspect of the therapeutic process from a responsiveness perspective, responsiveness is also crucial when it comes to deciding for themes and goals, and particular methods or interventions. Findings related to this notion that have been accumulated in our research group will be presented along with conceptual considerations. This will be complemented by some reflections from a basic psychology perspective.