Advances in Non-Type 2 Asthma in the Severe Cases: from molecular insights to novel treatment strategies.

Asthma is a prevalent pulmonary disease that affects nearly 300 million people worldwide and imposes a substantial economic burden. While medication can effectively control symptoms in some patients, severe asthma attacks, driven by airway-inflammation induced by environmental and infectious exposures, continue to be a major cause of asthma-related mortality. Heterogenous phenotypes of asthma include type 2 (T2) and non-T2 asthma. Non-T2 asthma is often observed in patients with severe and/or steroid-resistant asthma. This review will cover the molecular mechanisms, clinical phenotypes, causes and promising treatment of non-T2 severe asthma. Specifically, we will discuss the signaling pathways for non-T2 asthma including the activation of inflammasomes, interferon responses, and IL-17 pathways, and their contributions to the subtypes, progression, and severity of non-T2 asthma. Understanding the molecular mechanisms and genetic determinants underlying non-T2 asthma could form the basis for precision medicine in severe asthma treatment.

(19)F(α,n) thick target yield from 3.5 to 10.0 MeV.

Using a target of PbF2, the thick-target yield from the (19)F(α,n) reaction was measured from E(α)=3.5-10 MeV. From these results, we infer the thick-target neutron yields from targets of F2 and UF6 over this same alpha-particle energy range.

The incidence of glaucoma following paediatric cataract surgery: a 20-year retrospective study.

AIMS: To analyse the incidence of glaucoma in children undergoing cataract surgery and determine whether early surgery is associated with increased risk of glaucoma. METHODS: A retrospective chart review of all children aged 14 years or less who had surgery for congenital or developmental cataract at one unit over the last 20 years. The children were divided into three groups; group 1 consisting of children aged < or =50 days at surgery, group 2 those aged 51 days to 1 year, and group 3 aged 1-14 years. RESULTS: We identified a total of 104 eyes of 74 children. The medical records for 100 eyes (71 children) were available for review. In all, 17 eyes (12 children) were aged < or =50 days at surgery, none of which have developed glaucoma. Group 2 consisted of 28 eyes (17 children) with one patient developing glaucoma in both eyes 11 years after surgery. Group 3 consisted of 55 eyes (42 children), none of which have developed glaucoma. After a median follow-up period of 4.9 years (range 0.6-19.6 years, mean 6.4 +/- 5.2 years) 2% of eyes had developed glaucoma. There was no significant difference in the length of follow-up between groups (H=2.979, P=0.22, Kruskal-Wallis Test). CONCLUSIONS: There was a low incidence of glaucoma in our series and this was not increased in those having surgery in the first 6 weeks of life. Our findings contribute further evidence for the variability in prevalence of glaucoma after paediatric cataract extraction in the literature and suggest that factors other than age at surgery are important risk factors for this condition.

Ethnic variations in the incidence and outcome of severe retinopathy of prematurity.

BACKGROUND: The aim of this study was to assess the incidence and outcome of severe retinopathy of prematurity (ROP) among different ethnic groups in a geographically defined population in the U.K. Severe ROP was defined as any stage 3 or worse disease. METHODS: This was a retrospective study of children born over a 6-year period with a birth weight of 1250 g or less. Threshold ROP was treated with diode laser. RESULTS: Severe disease developed in 37 out of 355 neonates (10.4%) who underwent ROP screening. The difference in the incidence of severe ROP between infants of Caucasian and South Asian ethnic origin was not statistically significant: 10.2% vs. 10.8% (odds ratio = 1.06; 95% confidence interval: 0.44 to 2.57). This conclusion held after single-variable adjustment for birth weight, gestational age, and score on the Clinical Risk Index for Babies. The incidence of threshold ROP was 3% among infants of both Caucasian and South Asian ethnic origin. There was no significant difference in terms of visual outcome between the Caucasian and South Asian infants. INTERPRETATION: This study showed no statistical evidence for a difference in the incidence or outcome of severe ROP among infants of South Asian ethnic origin compared with those of Caucasian origin. Although the small numbers in our study mean that a clinically important difference cannot be excluded, it is very unlikely that the 5-fold higher incidence in Asian babies described in the literature is correct for the population from which our subjects were drawn.

Long-term results of closed nasolacrimal intubation in adults.

PURPOSE: Dacryocystorhinostomy (DCR) is the standard surgical treatment for adult nasolacrimal duct obstruction. There have been relatively few studies of closed nasolacrimal duct intubation in adults. The aim of this study was to determine rates of anatomic patency following this procedure. METHODS: The authors carried out a survey of all patients undergoing closed nasolacrimal duct intubation as a primary procedure over a period of 3 years and 4 months. There were 32 eligible patients of whom 20 attended for review. RESULTS: A total of 75% of these cases had patent drainage after follow-up of between 6 months and 3 years. The proportion of patients with persistent patency after intubation was the same regardless of length of follow-up. CONCLUSIONS: The minimally invasive procedure of lacrimal intubation may have a role in some adults with nasolacrimal duct obstruction.

Ocular manifestations of mosaic trisomy 22: a case report and review of the literature.

Mosaic trisomy 22 is rare, but can be compatible with prolonged life. Patients with mosaic trisomy 22 usually present with intrauterine growth retardation, mental retardation, failure to thrive, and craniofacial asymmetry. We report the case of a five-year-old boy who had a birth weight of 3.8 kg and normal developmental milestones. He presented with unilateral ocular manifestations of ptosis, double elevator palsy, high myopia, and choroidal coloboma involving the macula. Cytogenetic evaluation showed a low level of trisomy 22 in peripheral blood lymphocytes (1 in 100) and in cultured fibroblasts from a conjunctival biopsy of the affected eye (1 in 60). Our case demonstrates the value of chromosomal analysis of the tissues involved rather than just karyotyping of the blood lymphocytes to detect mosaicism in patients with localised and unilateral congenital malformations.

Trends in the incidence of severe retinopathy of prematurity in a geographically defined population over a 10-year period.

OBJECTIVE: To examine trends in the incidence of severe (> or =grade 3) retinopathy of prematurity (ROP) in infants with birth weight of < or =1250 g in a geographically defined population over a 10-year period. METHODS: An observational study was conducted of all infants who had a birth weight < or =1250 g and were born to mothers who were resident in the county of Leicestershire, United Kingdom, during the period January 1, 1990, to December 30, 1999. Cases were identified by the Trent Neonatal Survey. The incidence of severe ROP (> or =grade 3) was compared in 2 successive 5-year periods: 1990-1994 and 1995-1999. RESULTS: Comparing the first 5-year period (1990-1994) with the second (1995-1999), the total number of live births fell (60 789 vs 56 564). However, there was a significant increase in the number of births with birth weight < or =1250 g (including live and dead; 615 vs 734; live births only: 455 vs 556). Survival to 42 weeks of infants who were born at < or =1250 g was significantly better in the latter time period (203 vs 302; odds ratio [OR] for death: 0.54; 95% confidence interval [CI]: 0.39-0.75). The number of cases of severe ROP was 4 times higher during the second time period compared with the first (9 vs 36). A significantly increased risk for the development of severe ROP was seen during the second time period (OR: 2.92; 95% CI: 1.37-6.20). Even after allowing for the change in gestation induced by the improved survival during the second time period, the increased risk remained (OR: 2.81; 95% CI: 1.27-6.21). CONCLUSIONS: There is strong evidence that the incidence of severe ROP among infants with birth weight < or =1250 g increased in the latter half of the last decade. The increased risk seems to be independent of the increase in survival.

A study of heredity as a risk factor in strabismus.

AIMS: Inheritance is recognised to have a part in the aetiology of strabismus but previous studies have not adequately distinguished between different types of strabismus leading to wide variations in reported findings. The aim of this study was to investigate the importance of heredity in different types of strabismus. METHODS: The parents of children attending for treatment of strabismus over a one-month period were interviewed to identify relatives with a history of strabismus. A complete three-generation pedigree was established for 96 index cases who were classified into four groups: infantile esotropia (26 cases), accommodative esotropia (49 cases), anisometropic esotropia (15 cases), and exotropia (six cases). RESULTS: Forty-three of a total of 165 (26.1%) first degree relatives of patients with hypermetropic accommodative esotropia were affected. In contrast, 15 of a total of 101 (14.9%) first degree relatives of patients with infantile esotropia, eight of a total of 66 (12.1%) first degree relatives of patients with anisometropic esotropia, and one of a total of 25 (4%) first degree relatives of patients with exotropia were affected. Analysing the data using logistic regression with a random term for family showed a significantly higher proportion of affected first degree relatives in the accommodative group than in any of the other three diagnostic groups. CONCLUSION: A history of strabismus appears to be more common in hypermetropic accommodative esotropia than in infantile esotropia, anisometropic esotropia or exotropia. More detailed investigation of the role of heredity in the aetiology of accommodative esotropia is needed.

Exogenous Pseudomonas endophthalmitis: a cause of lens enucleation.

Pseudomonas aeruginosa eye infection, although uncommon, may be a devastating disease if not recognised and treated appropriately, especially in premature infants. The case is presented of a premature baby who lost her right eye from invasive exogenous Ps aeruginosa eye infection.

Cross polarized spectacles in photosensitive epilepsy.

PURPOSE: To investigate the role of cross polarized spectacles in the treatment of photosensitivity demonstrable by EEG. METHOD: Patients receiving an EEG who tested positive for photosensitivity were invited to participate in the study. The most sensitive light flicker frequency causing a photic response was determined for each patient. Stimulation was repeated with 2 different pairs of spectacles--1 conventionally polarized and the other cross polarized. An EEG was obtained in each case and reported by a neurophysiologist who was unaware of the identity of the 2 types of spectacles. RESULTS: We tested 19 patients, 8 to 18 years of age. Two patients did not benefit from either pair of glasses. In 17 patients, the photic response was greatly diminished or eliminated by polarizing spectacles. In 1 patient, conventional polarized glasses helped, but the cross polarized spectacles did not. In 6 patients, both types of spectacles were equally effective; in 10 patients, cross polarized spectacles were more effective than conventionally polarized spectacles. CONCLUSION: The role of cross polarized spectacles in the management of photosensitivity in a clinical situation merits further investigation.

Severe retinopathy of prematurity and its association with different rates of survival in infants of less than 1251 g birth weight.

BACKGROUND: There is controversy over whether improved survival of preterm infants has resulted in a higher incidence of severe (grade 3 or greater) retinopathy of prematurity (ROP). AIM: To compare survival rates and rates of > or = stage 3 ROP-that is, with a high risk of sequelae-in preterm infants in five English cities where, anecdotally, the incidence of ROP is reported to show considerable variation. METHODS: All infants of birth weight < 1500 g and or gestational age < 32 weeks, born in 1994 in one of the cities or transferred in within 48 hours, were studied. The populations were adjusted for case mix variation using CRIB (clinical risk index for babies, a disease severity scoring system). The incidence of severe ROP, the actual death rate, and that adjusted for disease severity were determined. RESULTS: The rate of severe ROP per 1000 births was higher in city 1 than in all the other cities. This increase in comparison with city 2 and city 4 was significant (city 1, 167 (95% confidence interval (CI) 96 to 260); city 2, 24 (6 to 59); city 4, 16 (1 to 84)). A significant difference was not seen between city 1 and cities 3 (23 (1 to 120)) and 5 (74 (21 to 79)). The relative risk of developing severe ROP in city 1 compared with all the other cities was 5.5 (2.5 to 11.9). The actual death rate per 1000 births in city 1 was significantly lower than that predicted by modelling death against CRIB score (city 1: actual 270; predicted 385 (95% CI 339 to 431)). In contrast, the other cities had actual death rates as predicted, or worse than predicted, by CRIB. INTERPRETATION: A significantly higher incidence of severe ROP was identified in one of the five cities studied. Variation in survival rates among high risk infants may explain this observation.

The therapy of amblyopia: an analysis comparing the results of amblyopia therapy utilizing two pooled data sets.

CONTEXT: We previously presented the results of an original pooled data set of 961 amblyopic patients who underwent patching therapy for amblyopia from 1965 to 1994 (study group 1). Three types of amblyopia were considered: anisometropic, anisometropic-strabismic, and strabismic. Analysis of this group's success was related to the age at which therapy was initiated, the type of amblyopia, and the depth of visual loss before treatment was begun. The purpose of the current study is to test the validity of these findings on a second group of 961 amblyopes employing the data set used by Woodruff and associates in their publications (study group 2). These 2 data sets, after adjustment to conform to the definitions of age, amblyopia, anisometropia, and similar items utilized in common between the 2 study groups, will be compared for the risk factors predictive of successful occlusion therapy. OUTCOME: As in the previous study, the success of occlusion therapy is defined as a visual acuity of 20/40 or better at the end of treatment. RESULTS: Success by the 20/40 criteria was achieved in 73.7% in study group 1 and in 59.9% in study group 2. By category, the rate of success in study group 1 was 77.2% in strabismic amblyopia, 67.2% in anisometropic-strabismic amblyopia, and 66.0% in anisometropic amblyopia. In study group 2, success was 61.2% in strabismic amblyopia, 51.2% in anisometropic-strabismic amblyopia, and 63.0% in anisometropic amblyopia. Study group 1 univariate analysis related success in each group to the age at which therapy was initiated, the type of amblyopia, and the depth of visual loss before treatment in each group. In study group 2, univariate analysis related success of occlusion therapy to age and the depth of visual loss before treatment. Type of amblyopia was not related to outcome success in this group. When the 2 data sets were pooled, the risk factors for success were age and depth of visual loss at onset of treatment. CONCLUSIONS: Factors that appeared closely related to a successful outcome of patching therapy were patient age and depth of visual loss before treatment. These conclusions further support the value of early detection and screening for amblyopia, its prevention, where possible, and its adequate and vigorous treatment when it is detected and diagnosed.