Janet Rimmer

Association between nasal and bronchial symptoms in subjects with persistent allergic rhinitis

Background:  The association between nasal and bronchial symptoms, and the course of bronchial responsiveness and airway inflammation in house dust mite sensitive persistent rhinitis over a prolonged time period has not been thoroughly explored.

β-lactam allergenic determinants: fine structural recognition of a cross-reacting determinant on benzylpenicillin and cephalothin

Background An appreciation of the structural heterogeneity of allergenic determinants on penicillins and cephalosporins reveals the importance of side‐chain groups and their involvement in many allergies to β‐lactam drugs. Although allergenic cross‐reactions between penicillins and cephalosporins are known to occur, the precise molecular bases of such recognitions and cross‐sensitivities have rarely been studied and identified.

Most Personal Exposure to House Dust Mite Aeroallergen Occurs during the Day

Background The bed is commonly regarded as the main site of house dust mite exposure; however this has not been directly established by continuous measurements. The objective of this study was to determine the pattern of personal exposure to mite aeroallergen over 24 hours. Methods 12 adults each collected 9 sequential samples (8 during the day, mean 115 mins, and one overnight, mean 514 mins) over 24 hours using a portable air-pump (2L/min) connected to an IOM filter located on the shoulder during the day and on the bed head overnight. Samples were analysed for mite allergen Der p 1 by ELISA. Location and activity were recorded. A mixed model analysis was performed to determine exposure as a function of 14 categories of activity. Results Personal aeroallergen exposure differed widely over time, both within and between subjects. The highest average exposure (1117 pg/m3, 95% CI: 289-4314) occurred on public transport and the lowest overnight in bed (45 pg/m3, 95% CI: 17-17), which contributed only 9.8% (95% CI: 4.4%-15.1%) of total daily exposure. Aeroallergens were not related to bed reservoirs. Conclusion The study challenges the current paradigm that the bed is the main site of HDM exposure and instead suggests most exposure occurs in association with domestic activity and proximity to other people. Effective mite interventions, designed to improve asthma outcomes, need to first identify and then address the multiple sources of aeroallergen exposure.

Antifungal therapy in the treatment of chronic rhinosinusitis : a meta-analysis

Background Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Because fungi were postulated as a potential cause of CRS in the late 1990s, contrasting articles have advocated and refuted the use of antifungal agents in its management. Although good research shows an interaction of the immune system with fungus in CRS, e.g., allergic fungal sinusitis (AFS), this does not imply that fungi are the cause of CRS or that antifungals will be effective in management. This study was designed to assess the potential advantage of either topical or systemic antifungal therapy in the symptomatic treatment of CRS to aid physicians in making informed decisions about treating patients with CRS. Methods A systematic review of the literature was performed with meta-analysis. All studies obtained from searches were reviewed and trials meeting the eligibility criteria were selected. CRS was defined using either the European Position Paper on Rhinosinusitis and Nasal Polyps or American Academy of Otolaryngology–Head and Neck Surgery criteria. Authors were contacted and original data were used for data analysis. Results Five studies investigating topical antifungals and one investigating systemic antifungals met the inclusion criteria. All trials were double blinded and randomized. Pooled meta-analysis showed no statistically significant benefit of topical or systemic antifungals over placebo. Symptoms scores statistically favored the placebo group for this outcome. Adverse event reporting was higher in the antifungal group. Conclusion Reported side-effects of antifungal therapies may outweigh any potential benefits of treatment based on this meta-analysis and the authors therefore do not advocate the use antifungal treatment in the management of CRS.

Targeting adenosine receptors in the treatment of allergic rhinitis: a randomized, double‐blind, placebo‐controlled study

Background There is evidence that adenosine plays a role in the pathogenesis of asthma and rhinitis; however, it is currently unclear whether adenosine receptors are useful therapeutic targets in the treatment of allergic airway diseases.

IgE Sequences in Individuals Living in an Area of Endemic Parasitism Show Little Mutational Evidence of Antigen Selection

Patterns of somatic mutation in IgE genes from allergic individuals have been a focus of study for many years, but IgE sequences have never been reported from parasitized individuals. To study the role of antigen selection in the evolution of the anti‐parasite response, we therefore generated 118 IgE sequences from donors living in Papua New Guinea (PNG), an area of endemic parasitism. For comparison, we also generated IgG1, IgG2, IgG3 and IgG4 sequences from these donors, as well as IgG1 sequences from Australian donors. IgE sequences had, on average, 23.0 mutations. PNG IgG sequences had average mutation levels that varied from 17.7 (IgG3) to 27.1 (IgG4). Mean mutation levels correlated significantly with the position of their genes in the constant region gene locus (IgG3 < IgG1 < IgG2 < IgG4). Interestingly, given the heavy, life‐long antigen burden experienced by PNG villagers, average mutation levels in IgG sequences were little different to that seen in Australian IgG1 sequences (19.2). Patterns of mutation provide clear evidence of antigen selection in many IgG sequences. The percentage of IgG sequences that showed significant accumulations of replacement mutations in the complementarity determining regions ranged from 22% of IgG3 sequences to 39% of IgG2 sequences. By contrast, only 12% of IgE sequences had such evidence of antigen selection, and this was significantly less than in PNG IgG1, IgG2 and IgG4 subclass sequences (P < 0.01). The anti‐parasite IgE response therefore has the reduced evidence of antigen selection that has previously been reported in studies of IgE sequences from allergic individuals.

Divergent human populations show extensive shared IGK rearrangements in peripheral blood B cells

We have analysed the transcribed immunoglobulin kappa (IGK) repertoire of peripheral blood B cells from four individuals from two genetically distinct populations, Papua New Guinean and Australian, using high-throughput DNA sequencing. The depth of sequencing data for each individual averaged 5,548 high-quality IGK reads, and permitted genotyping of the inferred IGKV and IGKJ germline gene segments for each individual. All individuals were homozygous at each IGKJ locus and had highly similar inferred IGKV genotypes. Preferential gene usage was seen at both the IGKV and IGKJ loci, but only IGKV segment usage varied significantly between individuals. Despite the differences in IGKV gene utilisation, the rearranged IGK repertoires showed extensive identity at the amino acid level. Public rearrangements (those shared by two or more individuals) made up 60.2% of the total sequenced IGK rearrangements. The total diversity of IGK rearrangements of each individual was estimated to range from just 340 to 549 unique amino acid sequences. Thus, the repertoire of unique expressed IGK rearrangements is dramatically less than previous theoretical estimates of IGK diversity, and the majority of expressed IGK rearrangements are likely to be extensively shared in individual human beings.

Symptoms of persistent allergic rhinitis during a full calendar year in house dust mite-sensitive subjects

Background:  Little is known about the natural course of persistent rhinitis symptoms over a prolonged period.

Sleep disturbance in persistent allergic rhinitis measured using actigraphy

BACKGROUND Tiredness, fatigue, and impaired quality of life are common in patients with persistent allergic rhinitis (PAR). These symptoms may also be associated with reduced sleep quality in individuals with rhinitis. OBJECTIVE To determine whether sleep disturbance can be detected using actigraphy in patients with PAR. METHODS Ten house dust mite-allergic rhinitic patients and 10 nonallergic nonrhinitic control subjects were studied for 5 consecutive days and night. Continuous activity monitoring during the study period using actigraphy was used to obtain markers of sleep quality, such as sleep onset, sleep duration, and sleep fragmentation. In addition, participants recorded in a sleep diary the time they went to bed, the time they went to sleep, the time they awoke, and the quality of their sleep. RESULTS Allergic rhinitic patients were found to have an increased fragmentation index value, indicative of reduced sleep quality and increased sleep disturbance, compared with the control group (P = .007). CONCLUSIONS Using actigraphy, we identified specific sleep disturbances in patients with PAR that may result in the increased tiredness, fatigue, and impaired quality of life typically experienced in such patients.

Real‐life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria

Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30–1500 IU/mL) and bodyweight (30–150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government‐subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR).