Burden of illness in blood eosinophilic phenotype COPD patients in New Zealand.

BACKGROUND: Real-world data on eosinophilic chronic obstructive pulmonary disease (COPD)'s clinical burden, in exacerbating/stable states, and the stability of blood eosinophil count (BEC) measurements are limited. We described measured BEC distributions among general practice COPD patients in New Zealand (NZ). METHODS: This retrospective cohort study utilized the NZ-HealthStat primary care database. Participants were aged ≥40 years, with ≥1 BEC 6 months following a COPD diagnosis code during 2011-2012. Descriptive analyses included examinations of BEC stability and association with COPD exacerbations/treatments/comorbidities. RESULTS: The most frequent COPD comorbidity was asthma (n = 1180/2909, 40.56%). Among COPD patients: 65% had BECs >150 cells/µL; 35% had BECs >300 cells/µL (non-mutually exclusive threshold categories). Treatment patterns were similar, except for more frequent inhaled corticosteroid (ICS)/long-acting beta2-agonist use in COPD patients with asthma history (51%) than those without (31%). Factors associated with BECs >150 cells/µL in participants without ICS treatment included Maori/Pacific ethnicity, obesity, oral corticosteroid (OCS) use, and exacerbation history. When stratified by asthma history, ICS treatment, and neutrophil count above/below 5000 cells/µL, geometric mean BECs ranged from 136.70 to 398.52 cells/µL. Exploratory analyses showed a fair-good COPD/BEC measurement stability over 12 months. CONCLUSIONS: Asthma was a common COPD comorbidity in NZ, particularly in Maori/Pacific patients. No overall relationship was observed between BEC/COPD exacerbations, which may reflect background ICS confounding. However, analyses in non-ICS treated participants suggested that Maori/Pacific patients with obesity and COPD, OCS treatment, exacerbation history, and/or elevated BECs are at the highest risk of COPD exacerbations. One BEC measurement appears a good indicator of a patient's BECs over time.

Long-Acting Bronchodilator Use in Chronic Obstructive Pulmonary Disease in Primary Care in New Zealand: A Retrospective Study of Treatment Patterns and Evolution Using the HealthStat Database.

PURPOSE: Long-acting bronchodilator (LABD) use is the mainstay of pharmacologic treatment for chronic obstructive pulmonary disease (COPD). Few studies describe evolving patterns of LABD use in the setting of changing inhaler availability and updated clinical guidelines. METHODS: A retrospective cohort study in New Zealand using the HealthStat general practice database (01/2014 to 04/2018). Eligible patients (aged ≥40 years) had COPD and ≥1 LABD prescription (long-acting muscarinic antagonist [LAMA] and/or long-acting ß2-agonist [LABA]) during the index period (05/2015 to 04/2016). Demographics and clinical characteristics of all LABD users (overall/by treatment) were described at baseline. Patients starting LABD treatment during the index period, termed "new" users, were also described, as was their treatment evolution over 24 months of follow-up. Yearly LABD initiation rates were assessed from 2015 to 2017, covering changes to Pharmaceutical Management Agency criteria and clinical guidelines. RESULTS: Across 2140 eligible patients, the most common index treatments were inhaled corticosteroid (ICS)/LABA (59.0%) and open triple therapy (LAMA+LABA+ICS; 26.7%). ICS/LABA therapy was highest in younger patients, with open triple therapy highest in older patients. Prior yearly exacerbation rates were lowest in those receiving monotherapy (LABA: 0.9/year; LAMA: 1.1/year) versus dual therapy (all 1.4/year) and open triple therapy (2.2/year). Of 312 new LABD users, ICS/LABA was the most common index treatment (69.6%), followed by LAMA monotherapy (16.0%). Continuous use with index treatment was 31.1% at 12 months and 13.5% at 24 months; mean time to treatment change was 175.5 and 244.1 days, respectively. Among patients modifying treatment at 24 months, 23.0% augmented, 7.0% switched, 45.6% re-started, and 24.4% discontinued/stepped down. Among patients initiating LABD each year from 2015 to 2017, LAMA prescription increased (17% to 46%) while ICS prescription remained stable (approximately 20%). CONCLUSION: Predominant use of ICS/LABA (05/2015 to 04/2016) reflects available LABDs and previous restrictions on LAMA use in New Zealand.

Rhinovirus-induced CCL17 and CCL22 in Asthma Exacerbations and Differential Regulation by STAT6.

The interplay of type-2 inflammation and antiviral immunity underpins asthma exacerbation pathogenesis. Virus infection induces type-2 inflammation-promoting chemokines CCL17 and CCL22 in asthma; however, mechanisms regulating induction are poorly understood. By using a human rhinovirus (RV) challenge model in human airway epithelial cells in vitro and mice in vivo, we assessed mechanisms regulating CCL17 and CCL22 expression. Subjects with mild to moderate asthma and healthy volunteers were experimentally infected with RV and airway CCL17 and CCL22 protein quantified. In vitro airway epithelial cell- and mouse-RV infection models were then used to define STAT6- and NF-κB-mediated regulation of CCL17 and CCL22 expression. Following RV infection, CCL17 and CCL22 expression was higher in asthma, which differentially correlated with clinical and immunological parameters. Air-liquid interface-differentiated primary epithelial cells from donors with asthma also expressed higher levels of RV-induced CCL22. RV infection boosted type-2 cytokine-induced STAT6 activation. In epithelial cells, type-2 cytokines and STAT6 activation had differential effects on chemokine expression, increasing CCL17 and suppressing CCL22, whereas NF-κB promoted expression of both chemokines. In mice, RV infection activated pulmonary STAT6, which was required for CCL17 but not CCL22 expression. STAT6-knockout mice infected with RV expressed increased levels of NF-κB-regulated chemokines, which was associated with rapid viral clearance. Therefore, RV-induced upregulation of CCL17 and CCL22 was mediated by NF-κB activation, whereas expression was differentially regulated by STAT6. Together, these findings suggest that therapeutic targeting of type-2 STAT6 activation alone will not block all inflammatory pathways during RV infection in asthma.

Characterization and burden of severe eosinophilic asthma in New Zealand: Results from the HealthStat Database.

BACKGROUND: This retrospective cohort study aimed to characterize epidemiology, medication use and healthcare resource utilization (HCRU) of patients diagnosed with severe eosinophilic asthma (SEA) compared to other patients with asthma in New Zealand. METHODS: Adult patients with asthma with no concurrent diagnosis of Chronic Obstructive Lung Disease (COPD) were identified from the HealthStat primary care database and the National Minimum Dataset using asthma diagnosis, hospital codes and prescriptions. Patients with SEA were identified using a 1-year baseline period (2011) and were those with: inhaled corticosteroid prescription above medium dose (including high dose) plus controller medication, ≥2 exacerbations, and eosinophils ≥300 cells/µl (or ≥150 in 6 weeks prior to index date); patients were followed for 1 year (2012). RESULTS: 160/3,276 (4.9%) asthmatics with available eosinophil counts met SEA criteria. Patients with SEA were more likely to be Maori, former smokers, have more comorbidities, higher mean BMI and higher neutrophil counts compared with other patients with asthma. In the follow up period, SEA patients had over 4 times as many exacerbations; incidence of exacerbations of the same frequency was highest in Maori patients. CONCLUSIONS: Compared with other patients with asthma, SEA patients had over 1.5 times as many respiratory treatment prescriptions and higher all-cause HCRU and total healthcare costs; asthma-related healthcare costs were 3.6 times greater.

Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation.

Rhinoviruses (RVs), which are the most common cause of virally induced asthma exacerbations, account for much of the burden of asthma in terms of morbidity, mortality, and associated cost. Interleukin-25 (IL-25) activates type 2-driven inflammation and is therefore potentially important in virally induced asthma exacerbations. To investigate this, we examined whether RV-induced IL-25 could contribute to asthma exacerbations. RV-infected cultured asthmatic bronchial epithelial cells exhibited a heightened intrinsic capacity for IL-25 expression, which correlated with donor atopic status. In vivo human IL-25 expression was greater in asthmatics at baseline and during experimental RV infection. In addition, in mice, RV infection induced IL-25 expression and augmented allergen-induced IL-25. Blockade of the IL-25 receptor reduced many RV-induced exacerbation-specific responses including type 2 cytokine expression, mucus production, and recruitment of eosinophils, neutrophils, basophils, and T and non-T type 2 cells. Therefore, asthmatic epithelial cells have an increased intrinsic capacity for expression of a pro-type 2 cytokine in response to a viral infection, and IL-25 is a key mediator of RV-induced exacerbations of pulmonary inflammation.

Characterisation of purified parvalbumin from five fish species and nucleotide sequencing of this major allergen from Pacific pilchard, Sardinops sagax.

IgE-mediated allergic reaction to seafood is a common cause of food allergy including anaphylactic reactions. Parvalbumin, the major fish allergen, has been shown to display IgE cross-reactivity among fish species consumed predominantly in Europe and the Far East. However, cross-reactivity studies of parvalbumin from fish species widely consumed in the Southern hemisphere are limited as is data relating to immunological and molecular characterisation. In this study, antigenic cross-reactivity and the presence of oligomers and isomers of parvalbumin from five highly consumed fish species in Southern Africa were assessed by immunoblotting using purified parvalbumin and crude fish extracts. Pilchard (Sardinops sagax) parvalbumin was found to display the strongest IgE reactivity among 10 fish-allergic consumers. The cDNA sequence of the beta-form of pilchard parvalbumin was determined and designated Sar sa 1.0101 (accession number FM177701 EMBL/GenBank/DDBJ databases). Oligomeric forms of parvalbumin were observed in all fish species using a monoclonal anti-parvalbumin antibody and subject's sera. Isoforms varied between approximately 10-13 kDa. A highly cross-reactive allergenic isoform of parvalbumin was identified and sequenced, providing a successful primary step towards the generation of a recombinant form that could be used for diagnostic and potential therapeutic use in allergic individuals.