A selective antagonist of histamine H₄ receptors prevents antigen-induced airway inflammation and bronchoconstriction in guinea pigs:involvement of lipocortin-1

BACKGROUND AND PURPOSE: Among the pathogenic mechanisms of asthma, a role for oxidative/nitrosative stress has been well documented. Recent evidence suggests that histamine H₄ receptors play a modulatory role in allergic inflammation. Here we report the effects of compound JNJ 7777120 (JNJ), a selective H4 receptor antagonist, on antigen-induced airway inflammation, paying special attention to its effects on lipocortin-1 (LC-1/annexin-A1), a 37 kDA anti-inflammatory protein that plays a key role in the production of inflammatory mediators.

EXPERIMENTAL APPROACH: Ovalbumin (OA)-sensitized guinea pigs placed in a respiratory chamber were challenged with antigen. JNJ (5, 7.5 and 10 mg.kg⁻¹) was given i.p. for 4 days before antigen challenge. Respiratory parameters were recorded. Bronchoalveolar lavage (BAL) fluid was collected and lung specimens taken for further analyses 1 h after antigen challenge. In BAL fluid, levels of LC-1, PGD2 , LTB4 and TNF-α were measured. In lung tissue samples, myeloperoxidase, caspase-3 and Mn-superoxide dismutase activities and 8-hydroxy-2-deoxyguanosine levels were measured.

KEY RESULTS: OA challenge decreased LC-1 levels in BAL fluid, induced cough, dyspnoea and bronchoconstriction and increased PGD2 , LTB4 and TNF-α levels in lung tissue. Treatment with JNJ dose-dependently increased levels of LC-1, reduced respiratory abnormalities and lowered levels of PGD2 , LTB4 and TNF-α in BAL fluid.

CONCLUSIONS AND IMPLICATIONS: Antigen-induced asthma-like reactions in guinea pigs decreased levels of LC-1 and increased TNF-α and eicosanoid production. JNJ pretreatment reduced allergic asthmatic responses and airway inflammation, an effect associated with LC-1 up-regulation.

Cigarette Smoke, Airway Epithelial Cells and Host Defence

In COPD inflammation driven by exposure to tobacco smoke results in impaired innate immunity in the airway and ultimately to lung injury and remodeling. To understand the biological processes involved in host interactions with cigarette derived toxins submerged epithelial cell culture is widely accepted as a model for primary human airway epithelial cell culture research. Primary nasal and bronchial epithelial cells can also be cultured in air-liquid interface (ALI) models. ALI and submerged culture models have their individual merits, and the decision to use either technique should primarily be determined primarily by the research hypothesis.

Cigarette smoke has gaseous and particulate matter, the latter constituent primarily represented in cigarette smoke extract (CSE). Although not ideal in order to facilitate our understanding of the responses of epithelial cells to cigarette smoke, CSE still has scientific merit in airway cell biology research. Using this model, it has been possible to demonstrate differences in levels of tight junction disruption after CSE exposure along with varied vulnerability to the toxic effects of CSE in cell cultures derived from COPD and control study groups.

Primary nasal epithelial cells (PNECs) have been used as an alternative to bronchial epithelial cells (PBECs). However, at least in subjects with COPD, PNECs cannot consistently substitute for PBECs. Although airway epithelial cells from patients with COPD exhibit a constitutional pro-inflammatory phenotype, these cells have a diminished inflammatory response to CSE exposure. COPD epithelial cells have an increased susceptibility to undergo apoptosis, and have reduced levels of Toll-like receptor-4 expression after CSE exposure, both of which may account for the reduced inflammatory response observed in this group.

The use of CSE in both submerged and ALI epithelial cultures has extended our understanding of the cellular mechanisms that are important in COPD, and helped to unravel important pathways which may be of relevance in its pathogenesis.

In-the-Bag Intraocular Lens Placement via Secondary Capsulorhexis with Radiofrequency Diathermy in Pediatric Aphakic Eyes

Pediatric ophthalmologists increasingly recognize that the ideal site for intraocular lens (IOL) implantation is in the bag for aphakic eyes, but it is always very difficult via conventional technique. We conducted a prospective case series study to investigate the success rate and clinical outcomes of capsular bag reestablishment and in-the-bag IOL implantation via secondary capsulorhexis with radiofrequency diathermy (RFD) in pediatric aphakic eyes, in which twenty-two consecutive aphakic pediatric patients (43 aphakic eyes) enrolled in the Childhood Cataract Program of the Chinese Ministry of Health were included. The included children underwent either our novel technique for secondary IOL implantation (with RFD) or the conventional technique (with a bent needle or forceps), depending on the type of preoperative proliferative capsular bag present. In total, secondary capsulorhexis with RFD was successfully applied in 32 eyes (32/43, 74.4%, age 5.6±2.3 years), of which capsular bag reestablishment and in-the-bag IOL implantation were both achieved in 30 eyes (30/43, 70.0%), but in the remaining 2 eyes (2/32, 6.2%) the IOLs were implanted in the sulcus with a capsular bag that was too small. Secondary capsulorhexis with conventional technique was applied in the other 11 eyes (11/43, 25.6%, age 6.9±2.3 years), of which capsular bag reestablishment and in-the-bag IOL implantation were both achieved only in 3 eyes(3/43, 7.0%), and the IOLs were implanted in the sulcus in the remaining 8 eyes. A doughnut-like proliferative capsular bag with an extensive Soemmering ring (32/43, 74.4%) was the main success factor for secondary capsulorhexis with RFD, and a sufficient capsular bag size (33/43, 76.7%) was an additional factor in successful in-the-bag IOL implantation. In conclusion, RFD secondary capsulorhexis technique has 70% success rate in the capsular bag reestablishment and in-the-bag IOL implantation in pediatric aphakic eyes, particularly effective in cases with a doughnut-like, extensively proliferative Soemmering ring. © 2013 Luo et al.

Effectiveness of a short message reminder in increasing compliance with pediatric cataract treatment:A randomized trial

Objective: Regular follow-up is essential to successful management of childhood cataract. We sought to assess whether a mobile phone short message service (SMS) for parents of children with cataract could improve follow-up adherence and the proportion of procedures performed in timely fashion. Design: Randomized, controlled trial. This trial is registered with ClinicalTrials.gov, NCT01417819. Participants: We included 258 parent-child pairs involved in the Childhood Cataract Program of the Chinese Ministry of Health. Methods: Participants were randomized (1:1) to a mobile phone SMS intervention or standard follow-up appointments. All participants were scheduled to attend <4 follow-up appointments according to the protocol. Parents in the intervention group received SMS automated reminders before scheduled appointments. The control group parents did not receive SMSs or any alternative reminder of scheduled appointments. Regular ocular examinations and analyses were performed by investigators masked to group allocation; however, study participants and the manager in charge of randomization and sending SMSs were not masked. Main Outcome Measures: Number of follow-up appointments attended, additional surgeries, laser treatments, changes in eyeglasses prescription, and occurrence of secondary ocular hypertension. Results: Among parent-child participants, 135 were randomly assigned to the SMS intervention and 123 to standard appointments. Attendance rates for the SMS group (first visit, 97.8%; second, 91.9%; third, 92.6%; fourth, 83%) were significantly higher than those for the control group (first visit, 87.8%; second, 69.9%; third, 56.9%; fourth, 33.3%). The increase in attendance rate for total number of follow-up visits with SMS reminders was 47.2% (relative risk [RR] for attendance, 1.47; 95% confidence interval [CI], 1.16-1.78; P = 0.003). The number needed to remind (NNR) to gain 1 additional visit by 1 child was 3 (95% CI, 1.8-4.2). A total of 247 clinical interventions were carried out in the SMS group and 134 in the control group (RR, 1.68; 95% CI, 1.37-1.99; P = 0.007). The NNR to result in 1 additional clinical intervention was 5 (95% CI, 3.5-6.5). Conclusions: The SMS reminders significantly improved follow-up adherence in pediatric cataract treatment. Using readily available mobile phone resources may be an effective and economic strategy to improve management of childhood cataract in China. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. © 2012 American Academy of Ophthalmology.

Determinants of pediatric cataract program outcomes and follow-up in a large series in Mexico.

PURPOSE:

To report determinants of outcomes and follow-up in a large Mexican pediatric cataract project.

SETTING:

Hospital Luis Sanchez Bulnes, Mexico City, Mexico.

METHODS:

Data were collected prospectively from a pediatric cataract surgery program at the Hospital Luis Sanchez Bulnes, implemented by Helen Keller International. Preoperative data included age, sex, baseline visual acuity, type of cataract, laterality, and presence of conditions such as amblyopia. Surgical data included vitrectomy, capsulotomy, complications, and use of intraocular lenses (IOLs). Postoperative data included final visual acuity, refraction, number of follow-up visits, and program support for follow-up.

RESULTS:

Of 574 eyes of 415 children (mean age 7.1 years +/- 4.7 [SD]), IOLs were placed in 416 (87%). At least 1 follow-up was attended by 408 patients (98.3%) (mean total follow-up 3.5 +/- 1.8 months); 40% of eyes achieved a final visual acuity of 6/18 or better. Children living farther from the hospital had fewer postoperative visits (P = .04), while children receiving program support had more visits (P = .001). Factors predictive of better acuity included receiving an IOL during surgery (P = .04) and provision of postoperative spectacles (P = .001). Predictive of worse acuity were amblyopia (P = .003), postoperative complications (P = .0001), unilateral surgery (P = .0075), and female sex (P = .045).

CONCLUSIONS:

The results underscore the importance of surgical training in reducing complications, early intervention before amblyopia (observed in 40% of patients) can develop, and vigorous treatment if amblyopia is present. The positive impact of program support on follow-up is encouraging, although direct financial support may pose a problem for sustainability. More work is needed to understand reasons for worse outcomes in girls.

Spectacle acceptance among secondary school students in rural China: the Xichang Pediatric Refractive Error Study (X-PRES)--report 5.

PURPOSE: To assess determinants of spectacle acceptance and use among rural Chinese children. METHODS: Children with uncorrected acuity < or = 6/12 in either eye and whose presenting vision could be improved > or = 2 lines with refraction were identified from a school-based sample of 1892 students. Information on obtaining glasses and the benefits of spectacles was provided to children, families, and teachers. Purchase of new spectacles and reasons for nonpurchase were assessed by direct inspection and interview 3 months later. RESULTS: Among 674 (35.6%) children requiring spectacles (mean age, 14.7 +/- 0.8 years), 597 (88.6%) were followed up. Among 339 children with no glasses at baseline, 30.7% purchased spectacles, whereas 43.2% of 258 children with inaccurate glasses replaced them. Most (70%) subjects paid US$13 to $26. Among children with bilateral vision < or = 6/18, 45.6% bought glasses. In multivariate models, presenting vision < 6/12 (P < 0.009), refractive error < -2.0 D (P < 0.001), and amount willing to pay for glasses (P = 0.01) were predictors of purchase. Reasons for nonpurchase included satisfaction with current vision (78% of those with glasses at baseline, 49% of those without), concerns over price or parental refusal (18%), and fear glasses would weaken the eyes (13%). Only 26% of children stated that they usually wore their new glasses. CONCLUSIONS: Many families in rural China will pay for glasses, though spectacle acceptance was < 50%, even among children with poor vision. Acceptance could be improved by price reduction, education showing that glasses will not harm the eyes, and parent-focused interventions.

Corneal hysteresis and axial length among Chinese secondary school children: the Xichang Pediatric Refractive Error Study (X-PRES) report no. 4.

PURPOSE: To evaluate the association between corneal hysteresis and axial length/refractive error among rural Chinese secondary school children. DESIGN: Cross-sectional cohort study. METHODS: Refractive error (cycloplegic auto-refraction with subjective refinement), central corneal thickness (CCT) and axial length (ultrasonic measurement), intraocular pressure (IOP), and corneal hysteresis (Reichert Ocular Response Analyzer) were measured on a rural school-based cohort of children. RESULTS: Among 1,233 examined children, the mean age was 14.7 +/- 0.8 years and 699 (56.7%) were girls. The mean spherical equivalent (n = 1,232) was -2.2 +/- 1.6 diopters (D), axial length (n = 643) was 23.7 +/- 1.1 mm, corneal hysteresis (n = 1,153) was 10.7 +/- 1.6 mm Hg, IOP (n = 1,153) was 17.0 +/- 3.4 mm Hg, and CCT (n = 1,226) was 553 +/- 33 microns. In linear regression models, longer axial length was significantly (P < .001 for both) associated with lower corneal hysteresis and higher IOP. Hysteresis in this population was significantly (P < .001) lower than has previously been reported for normal White children (n = 42, 12.3 +/- 1.3 mm Hg), when adjusting for age and gender. This difference did not appear to depend on differences in axial length between the populations, as it persists when only Chinese children with normal uncorrected vision are included. CONCLUSIONS: Prospective studies will be needed to determine if low hysteresis places eyes at risk for axial elongation secondary or if primary elongation results in lower hysteresis.

Visual disability, visual function, and myopia among rural chinese secondary school children: the Xichang Pediatric Refractive Error Study (X-PRES)--report 1.

PURPOSE: To evaluate visual acuity, visual function, and prevalence of refractive error among Chinese secondary-school children in a cross-sectional school-based study. METHODS: Uncorrected, presenting, and best corrected visual acuity, cycloplegic autorefraction with refinement, and self-reported visual function were assessed in a random, cluster sample of rural secondary school students in Xichang, China. RESULTS: Among the 1892 subjects (97.3% of the consenting children, 84.7% of the total sample), mean age was 14.7 +/- 0.8 years, 51.2% were female, and 26.4% were wearing glasses. The proportion of children with uncorrected, presenting, and corrected visual disability (< or = 6/12 in the better eye) was 41.2%, 19.3%, and 0.5%, respectively. Myopia < -0.5, < -2.0, and < -6.0 D in both eyes was present in 62.3%, 31.1%, and 1.9% of the subjects, respectively. Among the children with visual disability when tested without correction, 98.7% was due to refractive error, while only 53.8% (414/770) of these children had appropriate correction. The girls had significantly (P < 0.001) more presenting visual disability and myopia < -2.0 D than did the boys. More myopic refractive error was associated with worse self-reported visual function (ANOVA trend test, P < 0.001). CONCLUSIONS: Visual disability in this population was common, highly correctable, and frequently uncorrected. The impact of refractive error on self-reported visual function was significant. Strategies and studies to understand and remove barriers to spectacle wear are needed.

Strategies to improve the accuracy of vision measurement by teachers in rural Chinese secondary schoolchildren: Xichang Pediatric Refractive Error Study (X-PRES) report no. 6.

OBJECTIVE: To assess and improve the accuracy of lay screeners compared with vision professionals in detecting visual impairment in secondary schoolchildren in rural China. METHODS: After brief training, 32 teachers and a team of vision professionals independently measured vision in 1892 children in Xichang. The children also underwent vision measurement by health technicians in a concurrent government screening program. RESULTS: Of 32 teachers, 28 (87.5%) believed that teacher screening was worthwhile. Sensitivity (93.5%) and specificity (91.2%) of teachers detecting uncorrected presenting visual acuity of 20/40 or less were better than for presenting visual acuity (sensitivity, 85.2%; specificity, 84.8%). Failure of teachers to identify children owning but not wearing glasses and teacher bias toward better vision in children wearing glasses explain the worse results for initial vision. Wearing glasses was the student factor most strongly predictive of inaccurate teacher screening (P < .001). The sensitivity and specificity of the government screening program detecting low presenting visual acuity were 86.7% and 28.7%, respectively. CONCLUSIONS: Teacher vision screening after brief training can achieve accurate results in this setting, and there is support among teachers for screening. Screening of uncorrected rather than presenting visual acuity is recommended in settings with a high prevalence of corrected and uncorrected refractive error. Low specificity in the government program renders it ineffective.