Sensitization to minor cat allergen components is associated with type-2 biomarkers in young asthmatics.

BACKGROUND: Cat allergy is a major trigger of asthma world-wide. Molecular patterns of cat sensitization vary between individuals, but their relationship to inflammation in asthmatics has not been extensively studied. OBJECTIVE: To investigate the prevalence and levels of IgE antibodies against different cat allergen components and their relationship to type-2 inflammation and total IgE among young asthmatic subjects sensitized to furry animals. METHODS: Patients with asthma (age 10-35 years; n = 266) and IgE sensitization to cat, dog or horse extract (ImmunoCAP), were analysed for IgE to the cat allergen components Fel d 1 (secretoglobin), Fel d 2 (serum albumin), Fel d 4 and Fel d 7 (lipocalins). Independent associations between IgE-antibody concentrations, and fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, and total IgE were analysed by multiple linear regression after adjustment for possible confounders. RESULTS: The level of IgE against Fel d 2 was independently related to FeNO (P = .012) and total IgE (P < .001), and IgE against Fel d 4 associated with Β-Eos count (P = .009) and total IgE (P < .001). IgE antibodies against Fel d 1 or cat extract did not independently relate to these inflammatory markers (P = .23-.51). CONCLUSIONS: Levels of IgE to lipocalin (Fel d 4) and serum albumin (Fel d 2), but not to secretoglobin (Fel d 1) or cat extract, were independently associated with type-2 biomarkers and total IgE in young asthmatics. CLINICAL RELEVANCE: We suggest that measurement of IgE to minor cat allergen components may be useful when investigating asthma morbidity in cat allergic subjects.

Assessment of problematic severe asthma in children.

Assessment of problematic severe asthma in children should be performed in a step-wise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi-disciplinary assessment is performed to identify issues that may need attention, including comorbidities. Thirdly, the pattern of inflammation is assessed, and finally steroid responsiveness is documented. Based upon these four steps an optimal individualised treatment plan is developed. In this article the many gaps in our current knowledge in all these steps are highlighted, and recommendations for current clinical practice and future research are made. The lack of good data and the heterogeneity of problematic severe asthma still limit our ability to optimise the management on an individual basis in this small, but challenging group of patients.

The clinical benefit of evaluating health-related quality-of-life in children with problematic severe asthma.

AIM: To evaluate health-related quality-of-life (HR-QoL) and the asthma control test (ACT) in children with problematic severe asthma and those with controlled asthma and to identify whether clinical characteristics show correlations with these measurements. METHODS: This multicentre cross-sectional study included 93 children in total, 54 with problematic severe asthma and 39 age-matched with controlled asthma. Subjects completed the Paediatric Asthma Quality-of-Life Questionnaire as well as a standardized health questionnaire and the ACT. Objective measurements of exhaled nitric oxide, specific sensitization, pulmonary function and bronchial hyper-responsiveness to methacholine were also taken. RESULTS: HR-QoL was reduced in children with problematic severe asthma (5.4 vs. 6.7, p < 0.001), particularly for girls (5.1 vs. 5.6 for boys, p = 0.02), and their ACT scores were also lower (17 vs. 23, p < 0.001) compared with those of subjects with controlled asthma. A HR-QoL score <6.2 discriminated problematic severe asthma from controlled asthma with 85% sensitivity and 97% specificity, as did the ACT score <20 (79% sensitivity and 94% specificity). Objective measures and other clinical characteristics were weakly associated with HR-QoL or ACT score. CONCLUSION: Subjective measurements of HR-QoL and asthma control are both equally useful in differentiating children with problematic severe asthma from those with controlled asthma.

The Swedish National Airway Register (SNAR): development, design and utility to date.

BACKGROUND: The Swedish National Airway Register (SNAR) was initiated in 2013 to ensure and improve the quality of care for patients with asthma and COPD. AIM: To describe the development and design of SNAR, and to study the 2019 data to evaluate its potential utility related to improvement of quality of care. METHODS: SNAR includes data from patients with asthma (both children and adults) and COPD from primary, secondary and tertiary care, and also, for COPD inpatient care. Data on diagnostic investigations (e.g. spirometry, blood sample, skin prick test), symptom-scores, comorbidities and prescribed treatments are registered. The registrations are entered manually by healthcare professionals, or directly transferred from electronic medical records to a web-based platform. RESULTS: In 2019, 1000 clinics participated and data were directly transferred by about 88% of them. The register included data on 205,833 patients with asthma and 80,372 with COPD (of these, 5% had both diagnoses). Registrations of new patients and follow-up visits from primary and secondary/tertiary care in 2019 were completed for 75,707 patients with asthma (11,818 children <12 yr, 6545 adolescents 12-17 yr, and 57,344 adults >17 yr) and 38,117 with COPD. Depending on age and disease group, 43-77% had performed spirometry, 36-65% Asthma Control Test, and 60% COPD Assessment Test. The prevalence of current smoking was about 2% in adolescents, 10% in adults with asthma, and 34% in COPD. For these, smoking cessation support was offered to 27%, 38% and 51%, respectively. Overall, limited data were available on investigation of allergy, 6-min walk test, patient education and written treatment plans. Regarding asthma, sex-differences in disease management were evident. CONCLUSION: SNAR has cumulatively registered data from over 270,000 individuals, and the register is important for patients, caregivers, authorities, politicians and researchers to evaluate the effect of treatment and to ensure high and equal quality of care nationwide.

Clinical effects of purified air administered to the breathing zone in allergic asthma: A double-blind randomized cross-over trial.

BACKGROUND: Exposure to inhaled allergens is a pathogenetic factor in allergic asthma. However, most studies that previously looked at air cleaning devices have shown little or no effect on patients with perennial allergic asthma. AIMS AND OBJECTIVES: We examined a novel treatment using temperature regulated laminar airflow with a very low particle concentration directed to the breathing zone of teenagers and young adults with mild to moderate allergic asthma during night sleep. We hypothesised that the decreased allergen exposure during the night would have an effect on bronchial inflammation and quality of life. METHOD: Twenty-two patients (mean 18.8 years) were randomized to start with active or placebo treatment for 10 weeks. All patients received both active and placebo treatment with unfiltered air, with a 2-week wash-out period in between treatments. Maintenance treatment with inhaled corticosteroids was unaltered during the trial period. Health related quality of life (miniAQLQ) was the primary effectiveness measure. Exhaled nitric oxide (FeNO) and spirometry were also investigated. RESULTS: Active treatment resulted in an improved miniAQLQ compared to placebo (mean score 0.54, p<0.05, n=20). An effect on bronchial inflammation was also detected with significantly lower FeNO values during the active treatment period (mean -6.95 ppb, p<0.05, n=22). Both effects were evident after 5 weeks. The change in lung function was not statistically significant. CONCLUSION: Clean air, administered directly to the breathing zone during sleep, can have a positive effect on bronchial inflammation and quality of life in patients with perennial allergic asthma.

Salivary contribution to exhaled nitric oxide.

Dietary and metabolic nitrate is distributed from the blood to the saliva by active uptake in the salivary glands, and is reduced to nitrite in the oral cavity by the action of certain bacteria. Since it has been reported that nitric oxide may be formed nonenzymatically from nitrite this study aimed to determine whether salivary nitrite could influence measurements of exhaled NO. Ten healthy subjects fasted overnight and ingested 400 mg potassium nitrate, equivalent to approximately 200 g spinach. Exhaled NO and nasal NO were regularly measured with a chemiluminescence technique up to 3 h after the ingestion. Measurements of exhaled NO were performed with a single-breath procedure, standardized to a 20-s exhalation, at a flow of 0.15 L x s(-1), and oral pressure of 8-10 cmH2O. Values of NO were registered as NO release rate (pmol x s(-1)) during the plateau of exhalation. Exhaled NO increased steadily over time after nitrate load and a maximum was seen at 120 min (77.0+/-15.2 versus 31.2+/-3.0 pmol x s(-1), p<0.01), whereas no increase was detected in nasal NO levels. Salivary nitrite concentrations increased in parallel; at 120 min there was a four-fold increase compared with baseline (1.56+/-0.44 versus 0.37+/-0.09 mM, p<0.05). The nitrite-reducing conditions in the oral cavity were also manipulated by the use of different mouthwash procedures. The antibacterial agent chlorhexidine acetate (0.2%) decreased NO release by almost 50% (p<0.01) 90 min after nitrate loading and reduced the preload control levels by close to 30% (p<0.05). Sodium bicarbonate (10%) also reduced exhaled NO levels, but to a somewhat lesser extent than chlorhexidine acetate. In conclusion, salivary nitric oxide formation contributes to nitric oxide in exhaled air and a large intake of nitrate-rich foods before the investigation might be misinterpreted as an elevated inflammatory activity in the airways. This potential source of error and the means for avoiding it should be considered in the development of a future standardized method for measurements of exhaled nitric oxide.

Increased eosinophil transmigration after nasal allergen challenge in children with allergic asthma and rhinitis.

BACKGROUND: Eotaxin and interleukin-5 together provide the signal essential for eosinophil transmigration to airway tissue in allergic reactions. However, it is not known whether peripheral blood eosinophils (PBE) possess an increased transmigration capacity in vitro after allergen challenge in vivo before they leave the circulation. We aimed to determine whether PBE in cat-sensitized children have increased spontaneous and/or eotaxin-induced transmigration capacity in vitro, and to what extent allergen challenge alters this feature. METHODS: Fourteen cat-allergic children and four healthy controls underwent nasal challenge with cat-allergen. Blood samples were drawn prechallenge and at 2 h and 24 h postchallenge. We analyzed the in vitro transmigration of PBE, with and without eotaxin as a chemoattractant. We used a transmigration assay with fibronectin-coated membranes. Eosinophil cationic protein (ECP) and PBE counts were run in parallel. RESULTS: The spontaneous transmigration capacity of eosinophils in vitro was significantly higher at 2 h after allergen challenge (P < 0.01 vs. prechallenge) and returned to prechallenge levels at 24 h postchallenge (P < 0.02 vs. 2 h postchallenge). Addition of eotaxin further augmented the increased transmigration. In concordance, no accompanying changes were measured in the levels of eosinophils in blood or ECP in serum. Furthermore no spontaneous or eotaxin-induced eosinophil transmigration was detected in healthy controls. CONCLUSION: PBE possess increased spontaneous (and eotaxin-induced) capacity to transmigrate as early as 2 h after allergen challenge in allergic children, without accompanying signs of eosinophil activation in terms of increased PBE count or ECP level. This is probably due to the increased stage of activation of the eosinophil, often referred to as "priming".