Broadband wavelength and angle-resolved scattering characterization for nanophotonics investigations.

The characterization of scattered light is complex and relatively nonstandardized despite being of great importance to many optical technologies. While total scatter can be efficiently measured using integrating-sphere-based techniques, a detailed determination of the full bidirectional scattering distribution function is far more challenging, often requiring complicated and expensive equipment as well as substantial measurement time. Due to this, many research groups rely on simpler, angle-resolved scattering (ARS) measurements, yet these are typically carried out using a single wavelength source, therefore providing limited information. Here, we demonstrate a custom-built broadband angle-resolved optical spectrometer, which utilizes a supercontinuum white light laser source combined with a custom automated goniometer and a Si CCD array spectrometer in order to carry out broad spectral measurements of ARS. The use of a collimated supercontinuum allows for small area measurements that are often crucial for investigation of nanophotonic samples created using expensive fabrication techniques. The system has been tested and calibrated, and accuracy and reproducibility have been verified by integrating wavelength and ARS data over the angular range and comparing to calibrated integrating sphere measurements.

Corticosteroid responsiveness and clinical characteristics in childhood difficult asthma.

This study describes the clinical characteristics and corticosteroid responsiveness of children with difficult asthma (DA). We hypothesised that complete corticosteroid responsiveness (defined as improved symptoms, normal spirometry, normal exhaled nitric oxide fraction (F(eNO)) and no bronchodilator responsiveness (BDR <12%)) is uncommon in paediatric DA. We report on 102 children, mean+/-sd age 11.6+/-2.8 yrs, with DA in a cross-sectional study. 89 children underwent spirometry, BDR and F(eNO) before and after 2 weeks of systemic corticosteroids (corticosteroid response study). Bronchoscopy was performed after the corticosteroid trial. Of the 102 patients in the cross-sectional study, 88 (86%) were atopic, 60 (59%) were male and 52 (51%) had additional or alternative diagnoses. Out of the 81 patients in the corticosteroid response study, nine (11%) were complete responders. Of the 75 patients with symptom data available, 37 (49%) responded symptomatically, which was less likely if there were smokers in the home (OR 0.31, 95% CI 0.02-0.82). Of the 75 patients with available spirometry data, 35 (46%) had normal spirometry, with associations being BAL eosinophilia (OR 5.43, 95% CI 1.13-26.07) and high baseline forced expiratory volume in 1 s (FEV(1)) (OR 1.08, 95% CI 1.02-1.12). Of these 75 patients, BDR data were available in 64, of whom 36 (56%) had <12% BDR. F(eNO) data was available in 70 patients, of whom 53 (75%) had normal F(eNO). Airflow limitation data was available in 75 patients, of whom 17 (26%) had persistent airflow limitation, which was associated with low baseline FEV(1) (OR 0.93, 95% CI 0.90-0.97). Only 11% of DA children exhibited complete corticosteroid responsiveness. The rarity of complete corticosteroid responsiveness suggests alternative therapies are needed for children with DA.

Ultrastructure of the reticular basement membrane in asthmatic adults, children and infants.

Reticular basement membrane (RBM) thickening in asthma is considered to be the result of subepithelial fibrosis. Thus, the RBM in asthma should contain an excess of fibrils identified as interstitial collagen and the ratio of fibril to matrix should be increased above normal levels. Electron micrographs of the RBM were compared with those of interstitial collagen deeper in the bronchial wall using endobronchial biopsy specimens from adult asthmatics (aged 18-41 yrs (n = 10)), children with difficult asthma (aged 6-16 yrs (n = 10)), wheezy infants with reversible airflow limitation (aged 0.3-2 yrs (n = 10)) and age-matched nonasthmatic controls: 10 adults, nine children and nine symptomatic infants with normal lung function. Fibrils in the RBM were significantly thinner (median (range) width 39 (30-52) nm versus 59 (48-73) nm), and fewer fibrils were banded than in the interstitial collagen (ratio of banded to non-banded fibrils 0.08 (0-0.17) versus 0.22 (0-1.3)). The ratio of fibrils to matrix in the thickened RBM of asthmatics did not differ from that of their respective controls (1.34 (0.63-2.49) versus 1.18 (0.31-2.6)). The ratio of fibril to matrix in the thickened reticular basement membrane of asthmatics is normal, and, contrary to what is expected in fibrosis, the fibrils do not resemble those of interstitial collagen.

A video questionnaire identifies upper airway abnormalities in preschool children with reported wheeze.

BACKGROUND: Accurate characterisation of subjects is essential to interpret data from studies investigating preschool wheezing. AIM: To assess whether a video questionnaire (VQ) identifies upper airway abnormalities in preschool children with reported wheeze. METHODS: Forty three children (median age 17 months, range 3-58) undergoing fibreoptic bronchoscopy for clinical investigation of troublesome noisy breathing at a tertiary centre were studied. Parents were shown a VQ with four clips (wheeze, stridor, and two other upper respiratory noises) and chose the clip(s) resembling their child's main symptom. Doctor observed symptoms, parental reported symptoms, and symptoms identified on VQ were related to bronchoscopy. RESULTS: Thirty subjects had wheeze as the main symptom: 19 had doctor observed wheeze (DOW) and 11 had parental reported wheeze (RW). Parents of two of the subjects with RW identified wheeze alone on VQ and both had normal bronchoscopic findings. Five of the remaining nine subjects with RW had upper airway abnormalities at bronchoscopy. Parents of six subjects with RW identified a noise other than wheeze on VQ; four of these had upper airway abnormalities. Parents of two subjects with RW did not identify a noise on VQ; one had upper airway abnormalities. Of the 19 with DOW, nine parents identified wheeze alone on VQ, and all had a normal upper airway. Parents of nine subjects with DOW identified a noise other than wheeze as an equal or only symptom, (no noise identified in one), and five had upper airway abnormalities. CONCLUSION: A VQ helps to identify upper airway abnormalities in preschool children with a history of wheezing.

Airway inflammation in children with difficult asthma: relationships with airflow limitation and persistent symptoms.

BACKGROUND: The effective management and development of new treatments for children with difficult asthma requires investigation of the underlying airway pathology and its relationships with persistent symptoms and airflow limitation. METHODS: The density of immunologically distinct inflammatory cells and cells expressing interleukin (IL)-4, IL-5, and RANTES was determined in paraffin-embedded endobronchial biopsy specimens from 27 children with difficult asthma (6-16 years) following treatment with systemic corticosteroids. Eleven non-asthmatic children (7-16 years) acted as controls. Reticular basement membrane (RBM) thickness was also recorded and forced expiratory volume in 1 second (FEV(1)) and exhaled nitric oxide (FE(NO)) measured, the latter in asthmatic children only. RESULTS: RBM thickness was greater in the asthmatic than the control group (median (range) 7.4 (3.1-11.1) v 5.1 (3.5-7.5) microm, p = 0.02). No other significant tissue difference was seen, nor was there a difference between asthmatic subjects with daily symptoms after systemic corticosteroids and those who became asymptomatic. CD4+ T lymphocyte density was higher in asthmatic subjects with persistent airflow limitation (post-bronchodilator FEV(1)<80% predicted) than in those without (9.1 (5.5-13.6) v 3.5 (0.6-34.9)%, p = 0.027). Analysing all asthmatic subjects together, there were negative correlations between CD4+ T lymphocytes and both pre-bronchodilator FEV(1) (r = -0.57 (95% CI -0.79 to -0.23), p = 0.002) and post-bronchodilator FEV(1) (r = -0.61 (95% CI -0.81 to -0.29), p<0.001). There were no significant correlations between FE(NO) and inflammatory cells of any type. CONCLUSION: In children with difficult asthma treated with systemic corticosteroids, persistent airflow limitation is associated with a greater density of CD4+ T lymphocytes in endobronchial biopsy specimens.

The safety and quality of endobronchial biopsy in children under five years old.

BACKGROUND: Little is known about the airway pathology of wheezing disorders in infants and preschool children, partly owing to the difficulty of undertaking invasive studies in this age group. The safety of endobronchial biopsy and the quality of biopsies obtained were reviewed in infants and preschool children. METHODS: Case notes of children under five years of age who underwent bronchoscopy and endobronchial biopsy were reviewed. The safety of the procedure was compared in a control group matched for weight and age, undergoing bronchoscopy without endobronchial biopsy. A consultant histopathologist assessed biopsy quality. RESULTS: 33 patients (mean age 31 months, range 4 to 59) underwent bronchoscopy and endobronchial biopsy, and were matched with 33 controls (mean age 28 months, range 3 to 52). There was no significant difference between groups in the number, type, or severity of complications occurring during or after the procedure. Biopsies from 30 of the 33 subjects could be assessed. Reticular basement membrane was identified in all 30; inflammation could be assessed in 26; areas of smooth muscle were present in 23. CONCLUSIONS: In a group of preschool children undergoing bronchoscopy under general anaesthetic, performance of endobronchial biopsy carried no extra risk. The quality of biopsies obtained was usually sufficient to allow an assessment of remodelling and inflammation.