Proportion of Severe Asthma Patients Eligible for Mepolizumab Therapy by Age and Age of Onset of Asthma.
J Allergy Clin Immunol Pract. 2019 Jun 12;:
Authors: Comberiati P, McCormack K, Malka-Rais J, Spahn JD
BACKGROUND: Mepolizumab is an anti-IL-5 antibody approved for the treatment of severe eosinophilic asthma. However, the prevalence of patients with severe asthma eligible for mepolizumab remains unknown, especially among children.
OBJECTIVE: To determine, in a population of patients with severe asthma from a tertiary referral center, the proportion of patients with an eosinophilic phenotype who would be eligible for mepolizumab, when stratified for the age of onset of asthma, and the prevalence of phenotypic features that favor mepolizumab therapy.
METHODS: An extensive database of 245 adults and children referred for severe asthma was used. The prevalence of severe asthma was estimated by using the European Respiratory Society/American Thoracic Society criteria. Patients with an eosinophilic uncontrolled phenotype qualified for mepolizumab.
RESULTS: In our cohort, 216 (88%) had severe asthma. Based on blood eosinophils of either greater than or equal to 150 cells/μL or greater than or equal to 300 cells/μL, 61%/41% had an eosinophilic phenotype, while 49%/34% were eligible for mepolizumab therapy. A greater percentage of adults (60%/47% of adults with asthma onset in adulthood [AoA] and 48%/26% adults with childhood-onset asthma [<18 years, CoA]) were eligible compared with children (33%/24%, for eosinophil counts of ≥150 and ≥300 cells/μL, respectively; P < .05). Compared with adults, children had a similar number of exacerbations while having better lung function (P < .05). Among adults, those with AoA were older, were more likely to have nasal polyps (28% vs 5%; P < .05), and had higher blood eosinophil counts (272 vs 150 cells/μL; P < .05) compared with those with CoA, with no difference in lung function noted between the 2 groups. Subjects showing greater than or equal to 500 eosinophils/μL, a strong indicator for mepolizumab therapy, had more nasal polyps, higher inhaled steroid dose, lower lung function, and AoA predominance than did those with less than 500 eosinophils/μL (P < .05).
CONCLUSIONS: A smaller percentage of children with severe asthma were eligible for mepolizumab compared with their adult peers. Severe AoA has distinct phenotypic features that favor treatment with mepolizumab, including greater eosinophilia and nasal polyposis, in contrast to CoA, which appears to have fewer features of type 2 mucosal inflammation.
PMID: 31201938 [PubMed - as supplied by publisher]
Cockroach allergen component analysis of children with or without asthma and rhinitis in an inner-city birth cohort.
J Allergy Clin Immunol. 2019 Jun 12;:
Authors: Pomés A, Glesner J, Calatroni A, Visness CM, Wood RA, O'Connor GT, Kattan M, Bacharier LB, Wheatley LM, Gern JE, Busse WW, NIAID-funded Inner-City Asthma Consortium
BACKGROUND: Cockroach is one of the most important sources of indoor allergens that can lead to IgE sensitization and to the development of rhinitis and asthma.
OBJECTIVE: To perform a cockroach allergen component analysis to determine the allergens and antibody levels and patterns of sensitization that are associated with asthma and rhinitis.
METHODS: Antibody levels (IgE, IgG and IgG4) to total cockroach and to eight cockroach allergens were determined in two groups of cockroach sensitized 10-year old children with (n = 19) or without (n = 28) asthma and rhinitis. Allergen-specific antibody levels were measured in streptavidin ImmunoCAPs loaded with each of the recombinant allergens from groups 1, 2, 4, 5, 6, 7, 9, and 11, and total cockroach-specific IgE was measured using the i6 ImmunoCap.
RESULTS: IgE antibody levels to cockroach allergens and extract, but not IgG or IgG4, differed between subjects with and without asthma and rhinitis. Specifically, recognition of more cockroach allergens, with higher allergen-specific IgE, were associated with disease. Variable patterns of sensitization, with no immunodominant allergens, were found in both groups. There was a good correlation between the sum of allergen-specific IgE and total cockroach IgE (r = 0.86; p <0.001).
CONCLUSIONS: Component analysis of eight cockroach allergens revealed significant differences in IgE reactivity associated with the presence of asthma and rhinitis. Allergen-specific IgE titers and sensitization profiles were associated with asthma and rhinitis.
PMID: 31201891 [PubMed - as supplied by publisher]
Distinct Nasal Airway Bacterial Microbiota Differentially Relate to Exacerbation in Pediatric Asthma.
J Allergy Clin Immunol. 2019 Jun 12;:
Authors: McCauley K, Durack J, Valladares R, Fadrosh DW, Lin DL, Calatroni A, LeBeau PK, Tran HT, Fujimura KE, LaMere B, Merana G, Lynch K, Cohen RT, Pongracic J, Khurana Hershey GK, Kercsmar CM, Gill M, Liu AH, Kim H, Kattan M, Teach SJ, Togias A, Boushey HA, Gern JE, Jackson DJ, Lynch SV, NIAID-sponsored Inner-City Asthma Consortium
BACKGROUND: In infants, distinct nasopharyngeal bacterial microbiota differentially associate with incidence and severity of acute respiratory infection and childhood asthma development.
OBJECTIVE: We hypothesized that distinct nasal airway microbiota structures also exist in children with asthma and relate to clinical outcomes.
METHODS: Nasal secretion samples (n=3,122) collected post-randomization during the fall season from children with asthma (6-17 years, n=413) enrolled in a trial of omalizumab (anti-IgE) underwent 16S rRNA profiling. Statistical analyses with exacerbation as the primary outcome and RV infection and respiratory illnesses as secondary outcomes were performed. Using A549 epithelial cells, we assessed nasal isolates of Moraxella, Staphylococcus and Corynebacterium for their capacity to induce epithelial damage and inflammatory responses.
RESULTS: Six nasal airway microbiota assemblages, each dominated by Moraxella, Staphylococcus, Corynebacterium, Streptococcus, Alloiococcus or Haemophilus were observed. Moraxella and Staphylococcus-dominated microbiota were most frequently detected and exhibited temporal stability. Nasal microbiota dominated by Moraxella associated with increased exacerbation risk and eosinophil activation. Staphylococcus- or Corynebacterium-dominated microbiota associated with reduced respiratory illness and exacerbation events, while Streptococcus-dominated assemblages increased the risk of RV infection. Nasal microbiota composition remained relatively stable despite viral infection or exacerbation; only a few taxa belonging to the dominant genera exhibited relative abundance fluctuations during these events. In vitro, M. catarrhalis induced significantly greater epithelial damage and inflammatory cytokine expression (IL33 and IL8), compared with other dominant nasal bacterial isolates tested.
CONCLUSION: Nasal airway microbiota of children with asthma relate to the likelihood of exacerbation, RV infection, and respiratory illnesses during the fall season.
PMID: 31201890 [PubMed - as supplied by publisher]