Cytomegalovirus in primary immunodeficiency.

PURPOSE OF REVIEW: Cytomegalovirus (CMV) infection and disease are well described in the setting of secondary immunodeficiency. Less is known about CMV in the context of primary immunodeficiencies (PIDs), where inborn errors in one or more arms of the immune system result in variable degrees of CMV susceptibility. RECENT FINDINGS: PID presents unique challenges in the diagnosis and management of CMV disease. The clinical presentation of CMV in PID is often severe, accelerated by underlying immune dysregulation and iatrogenic immunosuppression. Here we describe the clinical significance of CMV infection in PID, the key components of immune defence against CMV and how these are affected in specific PIDs. CMV disease is under-recognized as a complication of common variable immunodeficiency (CVID). High rates of CMV end-organ disease, mortality, development of CMV resistance and prolonged antiviral use have been observed in individuals with CVID. SUMMARY: We recommend that clinicians tailor their approach to the individual based on their underlying immune deficit and maintain a high index of suspicion and low threshold for treatment. More research is required to improve stratification of CMV risk in PID, develop new diagnostic tools and manage end-organ disease in this cohort.

Managing Exacerbations in Thunderstorm Asthma: Current Insights.

Epidemic thunderstorm asthma (ETSA) occurs following a thunderstorm due to the interaction of environmental and immunologic factors. Whilst first reported in the 1980s, the world's largest event in Melbourne, Australia, on November 21, 2016 has led to a wealth of clinical literature seeking to identify its mechanisms, susceptibility risk factors, and management approaches. Thunderstorm asthma (TA) typically presents during an aeroallergen season in individuals sensitized to perennial rye grass pollen (RGP) in Australia, or fungus in the United Kingdom, in combination with meteorological factors such as thunderstorms and lightning activity. It is now well recognized that large pollen grains, which usually lodge in the upper airway causing seasonal allergic rhinitis (SAR), are ruptured during these events, leading to sub-pollen particles respirable to the lower respiratory tract causing acute asthma. The identified risk factors of aeroallergen sensitization, specifically to RGP in Australians with a history of SAR, and individuals born in Australia of South-East Asian descent as a risk factor for TA has been key in selecting appropriate patients for preventative management. Moreover, severity-determining risk factors for ETSA-related asthma admission or mortality, including pre-existing asthma or prior hospitalization, poor inhaled corticosteroid adherence, and outdoor location at the time of the storm are important in identifying those who may require more aggressive treatment approaches. Basic treatments include optimizing asthma control and adherence to inhaled corticosteroid therapy, treatment of SAR, and education regarding TA to increase recognition of at-risk days. Precision treatment approaches may be more beneficial in select individuals, including the use of allergen immunotherapy and even biologic treatment to mitigate asthma severity. Finally, we discuss the importance of environmental health literacy in the context of concerns surrounding the increased frequency of ETSA due to climate change and its implications for the frequency and severity of future events.

Response to Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma and Atopic Phenotypes.

PURPOSE: Improved understanding of characteristics that may influence treatment response across phenotypes may help guide treatment decisions. PATIENTS AND METHODS: This was a post hoc analysis of MENSA, a multicenter, randomized, double-blind, placebo-controlled trial (NCT01691521). Patients aged ≥12 years with severe eosinophilic asthma received mepolizumab (75 mg intravenously or 100 mg subcutaneously) or placebo, plus standard of care, every 4 weeks for 32 weeks. Outcomes assessed were the annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire (ACQ)-5 score. Subgroup analyses were performed by baseline blood eosinophil count (<150, ≥150-300, ≥300 cells/µL) within atopic subgroups (non-atopic [specific immunoglobulin E <0.35 kU/L], atopic [≥0.35-17.5 kU/L], strongly atopic [>17.5 kU/L]), and by house dust mite (HDM) sensitivity. RESULTS: Of 576 patients analyzed, 272 were non-atopic, 181 were atopic and 94 were strongly atopic; 29 had missing atopy data. In patients with blood eosinophil counts ≥300 cells/µL, mepolizumab versus placebo reduced clinically significant exacerbations by 74%, 43% and 25% in the non-atopic, atopic and strongly atopic subgroups. Similar reductions were observed in all atopic subgroups in other blood eosinophil count categories where there were sufficient patient numbers for analysis, except for non-atopic patients with baseline blood eosinophil counts of <150 cells/µL. Improvements in ACQ-5 scores of -0.75, -0.73 and -0.78 with mepolizumab versus placebo were observed in non-atopic, atopic and strongly atopic patients with blood eosinophil counts ≥300 cells/µL; consistent improvements in ACQ-5 were not observed in patients with blood eosinophil counts <150 or ≥150-300 cells/µL. Reductions in clinically significant exacerbations with mepolizumab versus placebo were also observed irrespective of sensitivity to HDMs. CONCLUSION: Mepolizumab was associated with a trend for reductions in clinically significant exacerbations and improved asthma control versus placebo in patients with severe eosinophilic asthma, irrespective of atopic status or HDM sensitivity.

Continued loss of asthma control following epidemic thunderstorm asthma.

BACKGROUND: Epidemic thunderstorm asthma (ETSA) severely affected Melbourne, Australia in November 2016. There is scant literature on the natural history of individuals affected by ETSA. OBJECTIVE: A multicentre 12-month prospective observational study was conducted assessing symptomatology and behaviors of ETSA-affected individuals. METHODS: We used a structured phone questionnaire to assess asthma symptom frequency, inhaled preventer use, asthma action plan ownership and healthcare utilization over 12 months since the ETSA. Analysis of results included subgroup analyses of the "current," "past," "probable," and "no asthma" subgroups defined according to their original 2016 survey responses. RESULTS: Four hundred forty-two questionnaires were analyzed. Eighty percent of individuals reported ongoing asthma symptoms at follow-up, of which 28% were affected by asthma symptoms at least once a week. Risk of persistent asthma symptoms was significantly higher in those with prior asthma diagnosis, current asthma, and probable undiagnosed asthma (all p < 0.01). Of 442 respondents, 53% were prescribed inhaled preventers, of which 51% were adherent at least 5 days a week. Forty-two percent had a written asthma action plan and 16% had sought urgent medical attention for asthma in the preceding year. CONCLUSIONS: Following an episode of ETSA, patients experience a pivotal change in asthma trajectory with both loss of asthma control and persistence of de novo asthma. Suboptimal rates of inhaled preventer adherence and asthma action plan ownership may contribute to asthma exacerbation risk and susceptibility to future ETSA episodes. Longer-term follow-up is needed to determine the extent and severity of this apparent change.

Impact of helminth infection on childhood allergic diseases in an area in transition from high to low infection burden.

BACKGROUND: The effect of helminth infections on allergic diseases is still inconclusive. Furthermore, the effect of helminth infections on childhood allergic diseases in a tropical area where prevalence of helminth infections has undergone dramatic changes is not well documented. OBJECTIVE: To investigate the relationship between allergic diseases and helminth infection in a cohort of schoolchildren in an area that has undergone dramatic changes in intensity of helminth infections. METHODS: Children attending grade 5 were recruited from 17 schools in Western Province of Sri Lanka. They were assessed for allergic diseases using the International Study of Asthma and Allergies in Childhood questionnaire. Their serum total IgE (tIgE) and allergen-specific IgE (sIgE) for five common aeroallergens were measured by ImmunoCAP® method and stools were examined for the presence of helminth infections. RESULTS: A total of 640 children (mean age 10 years) were recruited to the study. Of them, 33.7% had evidence of allergic disease and 15.5% had helminth infections. Majority of infections (68.9%) were of low intensity. A significant relationship between allergic disease and helminth infections was not observed, however, a trend toward protective role of helminth infections against allergic diseases was noted. Multivariate analysis showed helminth infections to be an independent predictor of high tIgE levels whereas allergic disease was not. Allergic sensitization (atopy) was a significant risk factor for allergic disease only among non-infected children (odds ratio 3.025, p = 0.022) but not in infected children. The ratio of sIgE to tIgE was higher in non-infected children. CONCLUSION: Though not significant, a reduced risk of allergy in helminth-infected children was observed in this population. A Decrease in intensity of helminth infections may have contributed to the reduced capacity of immune-modulation by helminths in this paediatric population.

Fluticasone furoate nasal spray: effective monotherapy for symptoms of perennial allergic rhinitis in adults/adolescents.

Intranasal corticosteroids are widely prescribed for the treatment of perennial allergic rhinitis (PAR). The purpose of this study was to evaluate the efficacy and tolerability of intranasal fluticasone furoate, a novel enhanced-affinity glucocorticoid, in patients > or =12 years of age with PAR in a global, randomized, double-blind, placebo-controlled, 6-week study. Patients (n = 302) received fluticasone furoate nasal spray (FFNS) 110 microg or vehicle placebo once daily (q.d.). The primary efficacy measure was mean change from baseline over the 6-week treatment period in daily reflective total nasal symptom score (TNSS). Secondary end points included mean change from baseline in total and individual reflective nasal and ocular symptom scores and in daily peak nasal inspiratory flow (PNIF). FFNS was significantly more effective than placebo in reducing daily reflective TNSS over the treatment period (least square [LS] mean difference, -1.256; p < 0.001). Significant improvements were also established in total ocular symptom score (LS mean difference, -0.506; p = 0.004 versus placebo) and in all individual nasal (p < 0.001) and ocular (p < 0.03) symptoms assessed in a reflective manner. Improvements in daily PNIF were significantly greater with FFNS than placebo (LS mean difference, 8.376 L/minute; p = 0.004). FFNS was well tolerated. In this study, FFNS 110 microg q.d. was well tolerated and effective in reducing the nasal and ocular symptoms of PAR in adult and adolescent patients > or =12 years of age.