Sputum biomarkers during acute severe asthma attacks in children-a case-control study.

AIM: To study sputum mediator profiles pattern in children with acute severe asthma, compared with stable asthma and healthy controls. The mechanisms of acute severe asthma attacks, such as biomarkers cascades and immunological responses, are poorly understood. METHODS: We conducted a prospective observational case-control study of children aged 5 to 17 years, who presented to hospital with an asthma attack. Children with stable asthma were recruited during outpatient asthma clinic visits. Control children without an asthma diagnosis were recruited from surgical wards. Sputum mediator profiles were measured, and sputum leukocyte differential cell counts were generated. RESULTS: Sputum data were available in 48 children (acute asthma; n = 18, stable asthma; n = 17, healthy controls; n = 13). Acute-phase biomarkers and neutrophil attractants such as IL-6 and its receptor, IL-8 and cytokines linked with bacterial signals, including TNF-R1 and TNF-R2, were elevated in asthma attacks versus stable asthma and healthy controls. T-cell attractant cytokines, associated with viral infections, such as CCL-5, CXCL-10 and CXCL-11, and CXCL-9 (secreted from eosinophils after a viral trigger) were also raised. CONCLUSION: Mediator profiles consistent with bacterial and viral respiratory infections, and T2 inflammation markers co-exist in the sputum of children with acute severe asthma attacks.

Fungal sensitization and positive fungal culture from sputum in children with asthma are associated with reduced lung function and acute asthma attacks respectively.

BACKGROUND: Sensitization to thermotolerant fungi, including filamentous fungi and Candida albicans, is associated with poor lung function in adults with severe asthma. Data in children are lacking. Environmental exposure to fungi is linked with acute severe asthma attacks, but there are few studies reporting the presence of fungi in the airways during asthma attacks. METHODS: We investigated the association between fungal sensitization and/or positive fungal sputum culture and markers of asthma severity in children with chronic and acute asthma. Sensitization was determined using serum-specific IgE and skin prick testing against a panel of five fungi. Fungal culture was focused towards detection of filamentous fungi from sputum samples. RESULTS: We obtained sensitization data and/or sputum from 175 children: 99 with chronic asthma, 39 with acute asthma and 37 controls. 34.1% of children with chronic asthma were sensitized to thermotolerant fungi compared with no children without asthma (p =< 0.001). These children had worse pre-bronchodilator lung function compared with asthmatics without sensitization including a lower FEV1 /FVC ratio (p < .05). The isolation rate of filamentous fungi from sputum was higher in children with acute compared with chronic asthma. CONCLUSIONS: Fungal sensitization is a feature of children with chronic asthma. Children sensitized to thermotolerant fungi have worse lung function, require more courses of systemic corticosteroids and have greater limitation of activities due to asthma. Asthma attacks in children were associated with the presence of filamentous fungi positive sputum culture. Mechanistic studies are required to establish whether fungi contribute directly to the development of acute asthma.

MUC5AC and a Glycosylated Variant of MUC5B Alter Mucin Composition in Children With Acute Asthma.

BACKGROUND: Diffuse airway mucus obstruction is an important feature of severe and fatal asthma. MUC5AC and MUC5B are the principal gel-forming mucins found in airway mucus. The mucin composition of airway mucus likely affects its functional properties. METHODS: We quantified the principal airway mucins MUC5AC and MUC5B in the sputum of age-matched children with acute and stable asthma and healthy control subjects by using Western blotting. RESULTS: Sputum samples from 38 children (13 with acute asthma, 15 with stable asthma, 10 control subjects) were obtained. Sputum MUC5AC concentrations were 7.6 µg/mL in control subjects, 22.4 µg/mL in those with stable asthma (P = .17), and 44.7 µg/mL in those with acute asthma (P < .05). MUC5B concentrations showed less variation, with 238.5, 208.4 and 165.9 µg/mL in control subjects, those with stable asthma, and those with acute asthma, respectively. The greater MUC5AC concentration in those with acute asthma resulted in a significantly altered MUC5B:MUC5AC ratio between control subjects and those with acute asthma (P < .05). Significant differences in MUC5B glycoforms were present between the groups, with the low-charge-only glycoform being found uniquely in those with acute asthma. CONCLUSIONS: Increased MUC5AC and the presence of a low-charge-only MUC5B glycoform significantly altered mucin composition in children with acute asthma. These changes may be important contributory factors to the airway mucus obstruction observed during acute asthma.

Comparison of Blood Eosinophil Numbers Between Acute Asthma and Stable Disease in Children with Preschool Wheeze.

Background: Preschool wheezing is common and many children experience exacerbations and are well in between. Raised blood eosinophils in older children are associated with exacerbation-prone wheeze, but there are currently no biomarkers to predict near-future exacerbations in preschoolers. There is evidence suggesting that eosinophils are acutely activated during an exacerbation using urinary markers, however, it is unknown whether blood eosinophil numbers fluctuate between the time of an exacerbation and stable disease. Objective: To investigate whether, in children with preschool wheeze, blood eosinophil numbers are different during an acute wheezing episode compared with periods of stable disease. Methods: Blood samples were taken from children aged 10 months to 6 years, presenting with acute, doctor-diagnosed wheeze, and tested for absolute leukocyte differential cell numbers. A repeat blood sample was obtained in a subset of children after full recovery. Main Outcome Measure: Difference between blood eosinophil counts during an acute wheezing episode and after recovery (stable disease) was also obtained. Results: Eighty-five children participated in this study, with 68 recruited during an acute wheezing episode (median absolute blood eosinophil numbers 0.10 × 109/L [range 0.00-2.41]) and 17 healthy controls. There was no significant difference in absolute blood eosinophil numbers between the acutely wheezy children when compared with the controls (median 0.17 × 109/L range 0.00-0.83). Absolute blood eosinophil numbers during stable disease were significantly greater (median 0.43 × 109/L; range 0.12 × 1.25 × 109/L) compared with periods of exacerbation (median 0.11 × 109/L range 0.01-1.10) in 20 children in whom paired blood samples were available. Absolute blood lymphocyte numbers were also higher during periods of stable disease, whereas absolute blood neutrophil numbers were higher during the exacerbation. Conclusions: Greater numbers of blood eosinophils are present during stable disease compared with the exacerbation state. This is an important consideration when planning future studies using blood eosinophils as a biomarker in wheezy preschool children.