Effect of fluticasone propionate/formoterol and fluticasone furoate/vilanterol on adolescents with chronic bronchial obstruction.

Background: The combination of an inhaled corticosteroid (ICS) and long-acting ß-agonist (LABA) (ICS/LABA) has shown superiority in improving lung function (FEV1) compared with an ICS alone. The clinical effect of a ICS/LABA combination depends on the fine-particle fraction and the pulmonary deposition. Objective: We sought to compare the efficacy of 2 combinations of an ICS and LABA, namely, fluticasone propionate (FP) and formoterol (FORM) (FP/FORM) and fluticasone furoate (FF) and vilanterol (VI) (FF/VI), in asthmatic adolescents with chronic bronchial obstruction. Methods: FP/FORM (125 µg/5 µg, 2 doses twice daily via the k-haler [Mundipharma, Cambridge, UK]) and FF/VI (92 µg/22 µg, once daily via the Ellipta inhaler [GlaxoSmithKline]) were administered to adolescents aged 12 to 17 years who required regular antiasthmatic medication and had a ratio of FEV1 to forced vital capacity (FEV1/FVC) less than -1.65 SD in a 2-sequence, 16-week crossover trial. The primary efficacy end point was change in FEV1 compared with baseline. Secondary end points were FEV1/FVC ratio, maximal expiratory flow at 50% of the FVC, impulse oscillometry indices respiratory resistance at 5 Hz (R5), difference between R5 and respiratory resistance at 20 Hz (R20), area of reactance, and Asthma Control Test score. Results: Both ICS/LABA combinations resulted in a significant improvement in FEV1 and maximal expiratory flow at 50% of the FVC z scores without any significant difference between FP/FORM and FF/VI, with 40% of patients with either treatment achieving a normal prebronchodilator FEV1/FVC z score. Neither area of reactance nor difference between R5 and R20 improved significantly with either treatment. Conclusion: Both ICS/LABA combinations demonstrated significant improvements in FEV1z score. More than one-third of the asthmatic adolescents with prolonged bronchial obstruction achieved a normal prebronchodilator FEV1/FVC ratio.

Small airway function in Finnish COVID-19 survivors.

Follow-up studies of COVID-19 patients have found lung function impairment up to six months after initial infection, but small airway function has not previously been studied. Patients (n = 20) hospitalised for a severe SARS-CoV-2 infection underwent spirometry, impulse oscillometry, and multiple measurements of alveolar nitric oxide three to six months after acute infection. None of the patients had small airway obstruction, nor increased nitric oxide concentration in the alveolar level. None of the patients had a reduced FEV1/FVC or significant bronchodilator responses in IOS or spirometry. In conclusion, we found no evidence of inflammation or dysfunction in the small airways.

Predictive value of childhood airway hyper-responsiveness to indirect stimuli: 10-year longitudinal study.

BACKGROUND: Airway hyper-responsiveness (AHR) is a common feature in asthma. The use of AHR in predicting active asthma or the persistence of AHR in childhood is poorly understood. By analyzing longitudinal connections including different measures of AHR, lung function, and inflammation markers, we sought to identify the best available method for predicting persistence of AHR and identification of later active asthma. METHODS: We tested 105 asthmatic children aged 3-7 years with fractional exhaled nitric oxide (FeNO), impulse oscillometry (IOS), and AHR evaluated by indirect methods (hypertonic saline and exercise challenge). Ten years later, 64 children participated in the follow-up visit and were tested with FeNO, IOS, spirometry, and methacholine challenge. At both study visits, blood samples were collected, and a questionnaire was completed. RESULTS: Asthma was in remission in 66% of patients at adolescence. AHR measured by hypertonic saline challenge at preschool age was associated with asthma symptoms (OR 10.2; 95% CI 2.8, 37.3) but not with AHR estimated with methacholine challenge 10 years later. AHR measured by exercise challenge was not associated with AHR or recent asthma symptoms in adolescence. Preschool eosinophilia continued until adolescence in 87% of patients but was not associated with AHR or subjective signs of asthma 10 years later. Wheezy preschoolers with atopy had a higher risk for AHR in adolescence (OR 4.1; 95% CI 1.0, 16.2). CONCLUSION: Results from hypertonic saline challenge are associated with persistent asthma symptoms even after a decade. AHR measured by indirect methods at preschool age did not predict AHR in adolescence.

Gal d 1-specific IgE predicts allergy to heated egg in Finnish children.

BACKGROUND: Allergen-specific IgE levels can be useful in predicting outcomes of oral food challenges, but optimal cutoff levels vary in different populations. The aim was to determine cutoff values for egg white- and Gal d 1-, Gal d 2-, Gal d 3-, and Gal d 4-specific IgE (sIgE) predicting positive oral heated egg challenges in 185 Finnish children and adolescents. METHODS: A total of 185 egg-sensitized patients (age: 1-19 years, median: 6.3, mean: 7.0 years) with suspected egg allergy underwent double-blind, placebo-controlled (n = 78), or open (n = 107) oral food challenges with heated egg white. Specific IgE levels to egg white, Gal d 1 (ovomucoid), Gal d 2 (ovalbumin), Gal d 3 (conalbumin), and Gal d 4 (lysozyme) were measured by ImmunoCAP and compared with challenge outcomes. RESULTS: Of the 185 challenges, 124 (67%) were positive. Gal d 1 sIgE levels were significantly higher in the challenge-positive (median 13.5 kU/L, mean 33.2 kU/L) than in the challenge-negative group (median 0.2 kU/L, mean 1.2 kU/L), P < 0.0001. The diagnostic capacity of sIgE to egg white and Gal d 2, 3, and 4 was clearly weaker. In ROC analysis, the AUC for egg white was 0.86, Gal d 2 0.84, Gal d 3 0.79, and Gal d 4 0.77. Sensitization to Gal d 1 with a cutoff of value of >3.7 kU/L predicted a positive challenge with a specificity of 95% and sensitivity of 78%. The likelihood ratio was 15.9. In ROC analysis, the area under the curve was 0.94 (95% CI, 0.91-0.97). With a cutoff value of >14 kU/L, all challenges were positive, and with a cutoff of <0.9 kU/L, 95% of the challenges were negative. In the children aged 1-5 years (n = 88), the cutoff for Gal d 1 was >3.8 kU/L, and in the children above 6 years of age (n = 97), it was >3.5 kU/L. CONCLUSION: Gal d 1-specific IgE is useful in distinguishing egg-sensitized patients with clinically reactive egg allergy from those tolerant of heated egg. The optimal cutoff point in a Finnish population of 185 children and adolescents was 3.7 kU/L with no significant difference between the younger and older age groups.

Component-resolved diagnosis in selecting patients for yellowjacket venom immunotherapy.

BACKGROUND: Venom immunotherapy is effective in preventing systemic allergic reactions (SARs), but the diagnosis of venom allergy is problematic. OBJECTIVE: To compare the performance of component-resolved diagnosis and conventional tests in patients referred for venom immunotherapy. METHODS: We measured serum-specific immunoglobulin E to yellowjacket and honeybee venoms (Ves v 1 and Ves v 5 and Api m 1), cross-reactive carbohydrate determinants, serum basal tryptase (ImmunoCAP, ThermoFisher Scientific, Uppsala, Sweden), and skin prick test reactions in 84 patients referred to receive venom immunotherapy. History of SAR and its severity were evaluated. RESULTS: Of the 78 patients with suspected yellowjacket venom (YJV) allergy, a history of SAR was confirmed in 47 (60%) and 31 (40%) had a non-SAR reaction. The most accurate tests to confirm venom allergy after a SAR were serum-specific immunoglobulin E to yellowjacket whole-venom extract spiked with Ves v 5 (area under the curve 0.87, 95% confidence interval 0.77-0.97, P < .001) and Ves v 5 (area under the curve 0.86, 95% confidence interval 0.76-0.96, P < .001). Sensitization to Ves v 1 was infrequent and its area under the curve was low (0.62, 95% confidence interval 0.47-0.76, P = .106). Sensitivity of the YJV skin prick test was 86%, but its specificity was low at 54%. Double sensitization to yellowjacket and honeybee occurred frequently in skin prick tests. Of the patients without a SAR, 26% showed a positive reaction to YJV in any serum test and 46% showed a positive reaction in skin tests. CONCLUSION: Specific immunoglobulin E to the YJV spiked with Ves v 5 confirmed the allergy after a SAR. A history of SAR should be confirmed before testing, because venom sensitization is frequent in other types of reactions.

Double-blind placebo-controlled challenge showed that peanut oral immunotherapy was effective for severe allergy without negative effects on airway inflammation.

AIM: This study examined the efficacy and the safety of peanut oral immunotherapy (OIT). METHODS: We recruited 60 patients aged six years to 18 years who had a moderate-to-severe reaction to a double-blind placebo-controlled peanut challenge: 39 received OIT during an eight-month build-up phase and maintenance phase and 21 controls avoided peanuts. We measured specific immunoglobulin E and G4 (IgE and IgG4) to peanuts and to Ara h 1, 2, 3, 8 and 9 and monitored adverse events, bronchial hyper-responsiveness (BHR) to methacholine and fractional concentrations of exhaled nitric oxide (FeNO). The median follow-up period was 30 months. RESULTS: Most (85%) of the OIT patients passed the build-up phase and 67% tolerated 5 g of peanuts during the post-treatment challenge. No controls were desensitised, with a risk ratio of 29 and 95% confidence interval of 1.9-455. During OIT, IgE to peanut, Ara h 1, 2 and 3 decreased and IgG4 increased. Consuming peanuts had no harmful effects on BHR or FeNO. The annual incidence rate of emergency visits during the follow-up period was 11% or 3.0 per 10 000 patient-days. CONCLUSION: Peanut OIT was efficacious in severe allergies without negative effects on airway inflammation, but unpredictable long-term reactions might occur.