Implementation of a Teledermatology Electronic Consultation Program to Improve the Care of Patients with Inflammatory Bowel Disease.

Introduction: Skin lesions are a common extraintestinal manifestation associated with inflammatory bowel disease (IBD), although they may also appear as a complication of IBD treatment. Prompt referral to the dermatologist can be very helpful in practice. Teledermatology complements the traditional in-person health care modality, improving access to dermatological care. Objective: To evaluate the impact of a store-and-forward teledermatology electronic consultation (e-consult) program on the care of IBD patients. Methods: A retrospective study assessing the outcomes of our teledermatology program over its first 2 years of implementation. Results: A total of 39 consultations involving 33 patients (69.2% women, mean age 39.6 years [12-63]) were conducted. The mean number of teleconsultations was 2.8 per month in the initial implementation stage: 33 consultations were carried out in patients with Crohn's disease and 6 in ulcerative colitis. Only 18% of the patients had an active flare-up. The most frequent reason for the e-consult was paradoxical psoriasiform lesions (n = 13, 33.3%), commonly related with anti-tumor necrosis factor agents (70% of the patients) and hidradenitis suppurativa (n = 4, 10.3%). Resolution was achieved in 87% of patients, with a mean waiting time of 4.7 days (0-14). Almost all patients (97%) were satisfied with our program, and considered the referral through the program to be appropriate (92%). Best valued features were the reduced waiting time and the coordinated approach between the two departments involved. Conclusions: Dermatology e-consult is an efficient and useful means of optimizing IBD patient care.

Airway Hyperresponsiveness, Inflammation, and Pulmonary Emphysema in Rodent Models Designed to Mimic Exposure to Fuel Oil-Derived Volatile Organic Compounds Encountered during an Experimental Oil Spill.

BACKGROUND: Fuel oil-derived volatile organic compounds (VOCs) inhalation is associated with accidental marine spills. After the Prestige petroleum tanker sank off northern Spain in 2002 and the Deepwater Horizon oil rig catastrophe in 2009, subjects involved in environmental decontamination showed signs of ongoing or residual lung disease up to 5 y after the exposure. OBJECTIVES: We aimed at investigating mechanisms driving persistent respiratory disease by developing an animal model of inhalational exposure to fuel oil-derived VOCs. METHODS: Female Wistar and Brown Norway (BN) rats and C57BL mice were exposed to VOCs produced from fuel oil mimicking the Prestige spill. Exposed animals inhaled the VOCs 2 h daily, 5 d per week, for 3 wk. Airway responsiveness to methacholine (MCh) was assessed, and bronchoalveolar lavage (BAL) and lung tissues were analyzed after the exposure and following a 2-wk washout. RESULTS: Consistent with data from human studies, both strains of rats that inhaled fuel oil-derived VOCs developed airway hyperresponsiveness that persisted after the washout period, in the absence of detectable inflammation in any lung compartment. Histopathology and quantitative morphology revealed the development of peripherally distributed pulmonary emphysema, which persisted after the washout period, associated with increased alveolar septal cell apoptosis, microvascular endothelial damage of the lung parenchyma, and inhibited expression of vascular endothelial growth factor (VEGF). DISCUSSION: In this rat model, fuel oil VOCs inhalation elicited alveolar septal cell apoptosis, likely due to DNA damage. In turn, the development of a peculiar pulmonary emphysema pattern altered lung mechanics and caused persistent noninflammatory airway hyperresponsiveness. Such findings suggest to us that humans might also respond to VOCs through physiopathological pathways different from those chiefly involved in typical cigarette smoke-driven emphysema in chronic obstructive pulmonary disease (COPD). If so, this study could form the basis for a novel disease mechanism for lasting respiratory disease following inhalational exposure to catastrophic fuel oil spills. https://doi.org/10.1289/EHP4178.

T Cells localize with proliferating smooth muscle alpha-actin+ cell compartments in asthma.

RATIONALE: Airway remodeling in asthma comprises increased airway smooth muscle (ASM), an alteration linked to airway hyperresponsiveness and disease severity. Experimental studies showed that T cells adhere to ASM through vascular cell adhesion molecule-1 (VCAM-1) and drive ASM growth through direct contact between the T cells and smooth muscle alpha-actin (alpha-SMA)(+) cells. OBJECTIVES: To support the hypothesis of a T-cell/alpha-SMA(+) cell contact mechanism of ASM remodeling in asthma, using bronchial biopsies. METHODS: We performed quantitative morphology on T cells, proliferating cell nuclear antigen (PCNA), alpha-SMA, and VCAM-1 on biopsies from subjects with moderate and severe asthma and healthy control subjects. MEASUREMENTS AND MAIN RESULTS: We demonstrate ASM cell proliferation and infiltration by T cells in proportion to severity in the subjects with asthma. T cells localized with alpha-SMA(+)PCNA(+) cells, suggesting direct intercellular contact and a relationship with alpha-SMA(+) cell proliferation. Furthermore, the subjects with asthma developed a proliferating compartment of subepithelial alpha-SMA(+), nonorganized airway contractile elements (NOACE), suggesting a phenotype gradient from undifferentiated cells to smooth muscle-like cells. T-cell juxtaposition events were also observed in this compartment and correlated to its mass. The subjects with asthma showed VCAM-1 expression in postcapillary venules and clusters of VCAM-1 immunoreactivity in ASM and NOACE, consistent with a role of VCAM-1 in T-cell/alpha-SMA(+) cell interaction. CONCLUSIONS: T cells may induce alpha-SMA(+) cell proliferation through direct intercellular contact. NOACE may in part contribute to ASM growth through differentiation and translocation of alpha-SMA(+) cells. The findings support the role of the T cell in ASM remodeling in asthma.

Desarrollo de un modelo murino de inflamación y remodelación de vías respiratorias en asma experimental / Development of a Murine Model of Airway Inflammation and Remodeling in Experimental Asthma

IntroducciónLa investigación de los mecanismos de enfermedad del asma y la identificación de nuevas dianas terapéuticas requieren modelos animales experimentales. En este trabajo presentamos los datos del desarrollo de un modelo murino de asma experimental que permite valorar de forma conjunta parámetros de inflamación y remodelación de las vías respiratorias mediante morfología cuantitativa.Material y métodosSe sensibilizó a ovoalbúmina a ratones Balb/c y se les realizó broncoprovocación con ovoalbúmina o excipiente 3 veces por semana durante 12 semanas.ResultadosEn el lavado broncoalveolar, los ratones del grupo de ovoalbúmina presentaron un incremento significativo de leucocitos totales, con una mediana (cuartiles 25–75) de 670,0células/ml·103 (376,2–952,5), frente a 40,0células/ml·103 (60,0–85,0) en controles (p=0,001), y de las fracciones eosinófila y linfocitaria en recuento diferencial. En secciones sagitales de los pulmones inflados a presión estandarizada, estos ratones mostraron hiperplasia de células caliciformes en el epitelio respiratorio —reacción de ácido peryódico de Schiff: 53,89 (36,26–62,84) frente a 0,66 (0,00–1,06)células/mm2 (p<0,001)—, densa infiltración inflamatoria mononuclear y eosinófila —hematoxilina-eosina: 32,87 (27,34–37,13) frente a 0,06 (0,00–0,20)eosinófilos/mm2 (p=0,002)—, infiltración subepitelial por mastocitos —azul de toluidina: 2,88 (2,00–3,28) frente a 0,28 (0,15–0,35)mastocitos/mm2 (p<0,001)—, incremento de la masa de tejido contráctil —inmunofluorescencia para alfaactina de músculo liso: 2,60 (2,28–2,98) frente a 1,08 (0,93–1,16), adimensional (p<0,001)— e incremento del depósito de matriz extracelular (tricrómico de Masson: 2,18 (1,85–2,80) frente a 0,50 (0,37–0,65), adimensional (p<0,001)—.ConclusionesLos datos aportados configuran un modelo de asma experimental inducida por exposición alergénica prolongada, con desarrollo y evaluación integrada de inflamación y remodelación de vías respiratorias(AU)

Background and ObjectiveExperimental animal models are necessary for studying asthma disease mechanisms and for identifying new therapeutic targets. We present a murine model of experimental asthma that allows integrated, quantitative assessment of airway inflammation and remodeling.Material and MethodsBALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA or vehicle 3 times per week for 12 weeks.ResultsOn bronchoalveolar lavage, the OVA-sensitized mice had significantly higher total leukocyte counts, with a median (Q25–Q75) of 670.0cells/mL×103 (376.2, 952.5) in comparison with 40.0cells/mL×103 (60.0–85.0) in controls (P=.001), and higher eosinophil and differential lymphocyte counts. In sagittal sections of lungs inflated to a standard pressure, the OVA-sensitized animals showed goblet cell hyperplasia in the respiratory epithelium (periodic acid-Schiff staining, 53.89 [36.26–62.84]cells/mm2 vs 0.66 [0.00–1.06]cells/mm2, P<.001), dense mononuclear and eosinophilic inflammatory infiltrates (hematoxylin-eosin, 32.87 [27.34–37.13]eosinophils/mm2 vs 0.06 [0.00–0.20]eosinophils/mm2, P=.002), subepithelial infiltration by mast cells (toluidine blue, 2.88 [2.00–3.28] mast cells/mm2 vs 0.28 [0.15–0.35] mast cells/mm2, P<.001), increased contractile tissue mass (immunofluorescence analysis for α-smooth-muscle actin, 2.60 [2.28–2.98] vs 1.08 [0.93–1.16], dimensionless, P<.001) and enhanced extracellular matrix deposition (Masson's trichrome, 2.18 [1.85–2.80] vs 0.50 [0.37–0.65], dimensionless, P<.001).ConclusionsOur dataset describes an experimental model of asthma which is driven by prolonged allergen exposure and in which airway inflammation and remodeling develop and are assessed together(AU)

[Development of a murine model of airway inflammation and remodeling in experimental asthma]. / Desarrollo de un modelo murino de inflamación y remodelación de vías respiratorias en asma experimental.

BACKGROUND AND OBJECTIVE: Experimental animal models are necessary for studying asthma disease mechanisms and for identifying new therapeutic targets. We present a murine model of experimental asthma that allows integrated, quantitative assessment of airway inflammation and remodeling. MATERIAL AND METHODS: BALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA or vehicle 3 times per week for 12 weeks. RESULTS: On bronchoalveolar lavage, the OVA-sensitized mice had significantly higher total leukocyte counts, with a median (Q25-Q75) of 670.0 cells/mL x 10(3) (376.2, 952.5) in comparison with 40.0 cells/mL x 10(3) (60.0-85.0) in controls (P=.001), and higher eosinophil and differential lymphocyte counts. In sagittal sections of lungs inflated to a standard pressure, the OVA-sensitized animals showed goblet cell hyperplasia in the respiratory epithelium (periodic acid-Schiff staining, 53.89 [36.26-62.84]cells/mm(2) vs 0.66 [0.00-1.06]cells/mm(2), P<.001), dense mononuclear and eosinophilic inflammatory infiltrates (hematoxylin-eosin, 32.87 [27.34-37.13]eosinophils/mm(2) vs 0.06 [0.00-0.20]eosinophils/mm(2), P=.002), subepithelial infiltration by mast cells (toluidine blue, 2.88 [2.00-3.28] mast cells/mm(2) vs 0.28 [0.15-0.35] mast cells/mm(2), P<.001), increased contractile tissue mass (immunofluorescence analysis for alpha-smooth-muscle actin, 2.60 [2.28-2.98] vs 1.08 [0.93-1.16], dimensionless, P<.001) and enhanced extracellular matrix deposition (Masson's trichrome, 2.18 [1.85-2.80] vs 0.50 [0.37-0.65], dimensionless, P<.001). CONCLUSIONS: Our dataset describes an experimental model of asthma which is driven by prolonged allergen exposure and in which airway inflammation and remodeling develop and are assessed together.

Genotoxicity associated to exposure to Prestige oil during autopsies and cleaning of oil-contaminated birds.

After the accident involving the oil tanker Prestige in November 2002 near 63,000 tons of heavy oil reached Galician coast (Northwest of Spain). This unleashed a large movement of volunteers to collaborate in several cleaning tasks. The aim of this study was to determine whether handling of Prestige oil-contaminated birds during autopsies and cleaning may have resulted in genotoxic damage. We have also evaluated the possible influence of DNA repair genetic polymorphisms (XRCC1 codons 194 and 399, XRCC3 codon 241 and APE1 codon 148) on susceptibility to the genotoxic effects evaluated. Exposure levels were analysed by determining volatile organic compounds in air samples. Peripheral blood samples were obtained from 34 exposed and 35 controls, and comet assay and micronucleus (MN) test were carried out. Genotyping was performed following PCR-RFLP procedures. Results obtained have shown significantly higher DNA damage, but not cytogenetic damage, in exposed individuals than in controls, related to time of exposure. Among exposed individuals, carriers of the variant alleles XRCC1 399Gln and APE1 148Glu have shown altered DNA damage with regard to wild-type homozygotes, suggesting exposure-genotype interactions. No effect of the DNA repair genetic polymorphisms analysed was observed in the MN test.