Blood eosinophil counts rarely reflect airway eosinophilia in children with severe asthma.

BACKGROUND: The inflammatory phenotypes of severe asthma in adults may be reflected in peripheral blood. If this were true in children with severe therapy-resistant asthma (STRA), invasive tests could be avoided. At the moment there is no conclusive evidence in children. METHODS: All patients underwent blood tests, exhaled nitric oxide (FeNO), sputum induction, bronchoalveolar lavage (BAL) and endobronchial biopsy (EB). RESULTS: Sixty-three (71.6%) patients had a normal blood profile and only 1/88 had a combined blood eosinophilia and neutrophilia. 76/88 (86%) had normal blood eosinophils, but of these, 84% had airway eosinophilia in either BAL (n = 43;66%) or EB (n = 41;79%). In children with STRA blood eosinophilia was associated with airway eosinophilia. However, normal blood eosinophil levels did not exclude airway eosinophilic inflammation. CONCLUSIONS: Peripheral blood counts are not reliable in characterising airway inflammation in severe asthmatic children exposed to high dose steroid therapy, therefore bronchoscopy with BAL should be considered.

The complexities of defining atopy in severe childhood asthma.

BACKGROUND: Defining atopy in children with severe, therapy-resistant asthma is complex. There is currently no gold standard test; both skin prick testing (SPT) and allergen-specific IgE (sIgE) are used. Furthermore, atopy is increasingly considered to be a spectrum, not an all-or-none phenomenon. HYPOTHESIS: SPTs and sIgE cannot be used interchangeably, and if both tests are not performed, opportunities for intervention will be missed. Furthermore, the severity of atopy will be defined differently by the two tests. METHODS: Cross-sectional study of 47 children with severe, therapy-resistant asthma, mean age 11.8 years, range 5.3-16.6 years, who underwent SPT, and measurement of total and sIgE as part of their clinical work-up. RESULTS: Overall, 42/47 (89%) were atopic (defined as either one positive SPT or sIgE). There was 98% concordance between the two tests in classifying atopy. When each allergen was considered individually, in 40/200 (20%), the SPT and sIgE results were discordant, most commonly in 25/200 (12.5%), the SPT was negative and the sIgE was positive. House dust mite and cat sensitization were more likely detected by sIgE, but dog sensitization by SPT. When atopy was quantified, the sum of sIgEs compared with the sum of SPT weal diameter showed a moderate correlation (r(2) =0.44, P<0.001). Total IgE increased with an increasing number of positive sIgEs (P=0.028), but not significantly with increasing numbers of positive SPTs. CONCLUSION AND CLINICAL RELEVANCE: SPT and sIgE identify group prevalence of atopy equally well; however, for individual allergens, concordance is poor, and when used to quantify atopy, SPTs and sIgE were only moderately correlated. In a clinical setting, if allergen avoidance is contemplated in children with severe, therapy-resistant asthma, both tests should be performed in order to detect sensitization.

TSLP polymorphisms are associated with asthma in a sex-specific fashion.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion. METHODS: We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of children with asthma in Costa Rica. Significant findings were replicated in whites and African-American participants in the Childhood Asthma Management Program, in African-Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children's Health Study, and in whites in the Framingham Heart Study (FHS). MAIN RESULTS: Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (P values of 2 × 10(-5) and 1 × 10(-5) , respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (P = 3 × 10(-6) ). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (P = 2 × 10(-4) ). Findings for rs2289276 were consistent in all cohorts except the FHS. CONCLUSIONS: TSLP variants are associated with asthma in a sex-specific fashion.

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.

The intermetatarsophalangeal bursa--its significance in Morton's metatarsalgia.

The intermetatarsophalangeal bursa was investigated by dissection, radiography and injection. In the web spaces between the second and third and the third and fourth digits the bursa lies superior to the transverse metatarsal ligament but projects distally to it, closely applied to the neurovascular bundle. Tissue from the web spaces of patients with classical Morton's metatarsalgia often shows lymphocytic infiltration, with additional fibrinoid necrosis of the bursal wall. It is suggested that inflammatory changes in this bursa could account for the pathological and histological findings in this condition. The bursa in the most lateral web space does not extend beyond the ligament and is not in contact with the neurovascular bundle, which may explain the rarity of symptoms in this space.

Osteotomy in the treatment of osteoarthritis of the first carpometacarpal joint.

Degenerative changes of the first carpometacarpal joint commonly cause pain, weakness and adduction deformity. Many patients respond to conservative treatment, but in resistant cases an abduction wedge osteotomy of the base of the first metacarpal has been found to relieve symptoms with less complications than other operations. Twenty-one patients with 23 osteotomies have been reviewed, with a follow-up from 2 to 17 years. All have had lasting relief from pain and consider that they have full function, with no stiffness or limited abduction. Osteotomy is indicated mainly for cases where the arthritis is confined to the carpometacarpal joint, but also relieves pain in cases of peritrapezial arthritis.

Industrial hand injuries in Pacific Island immigrants.

There is a disturbingly high incidence of heavy machinery, industrial hand mutilation, involving recent Pacific Island immigrants many of whom have a poor comprehension of English. A survey of cases admitted to the Hutt Hospital during eight monts of 1973, showed a proportionately greater incidence of severe injuries amongst these immigrants, and indicates that one causative factor is unsuitable selection of works for this dangerous machinery, coupled with inadequate instruction in its use and safety precautions.

Conservative treatment of digit amputations.

A conservative regime for distal digit amputations allowing healing under vaseline gauze has much to recommend it, being simple and allowing rapid healing with few complications. Secondary distal amputations for gangrene and sepsis also heal rapidly if left open. A consecutive series of 55 amputations treated in this way is described.

Impaired innate interferon induction in severe therapy resistant atopic asthmatic children.

Deficient type I interferon-ß and type III interferon-λ induction by rhinoviruses has previously been reported in mild/moderate atopic asthmatic adults. No studies have yet investigated if this occurs in severe therapy resistant asthma (STRA). Here, we show that compared with non-allergic healthy control children, bronchial epithelial cells cultured ex vivo from severe therapy resistant atopic asthmatic children have profoundly impaired interferon-ß and interferon-λ mRNA and protein in response to rhinovirus (RV) and polyIC stimulation. Severe treatment resistant asthmatics also exhibited increased virus load, which negatively correlated with interferon mRNA levels. Furthermore, uninfected cells from severe therapy resistant asthmatic children showed lower levels of Toll-like receptor-3 mRNA and reduced retinoic acid inducible gene and melanoma differentiation-associated gene 5 mRNA after RV stimulation. These data expand on the original work, suggesting that the innate anti-viral response to RVs is impaired in asthmatic tissues and demonstrate that this is a feature of STRA.

Fitness to fly testing in term and ex-preterm babies without bronchopulmonary dysplasia.

BACKGROUND: During air flight, cabin pressurisation produces an effective fraction of inspired oxygen (FiO(2)) of 0.15. This can cause hypoxia in predisposed individuals, including infants with bronchopulmonary dysplasia (BPD), but the effect on ex-preterm babies without BPD was uncertain. The consequences of feeding a baby during the hypoxia challenge were also unknown. METHODS: Ex-preterm (without BPD) and term infants had fitness to fly tests (including a period of feeding) at 3 or 6 months corrected gestational age (CGA) in a body plethysmograph with an FiO(2) of 0.15 for 20 min. A 'failed' test was defined as oxygen saturation (SpO(2)) <90% for at least 2 min. RESULTS: 41 term and 30 ex-preterm babies (mean gestational age 39.8 and 33.1 weeks, respectively) exhibited a significant median drop in SpO(2) (median -6%, p<0.0001); there was no difference between term versus ex-preterm babies, or 3 versus 6 months. Two term (5%) and two ex-preterm (7%) babies failed the challenge. The SpO(2) dropped further during feeding (median -4% in term and -2% in ex-preterm, p<0.0001), with transient desaturation (up to 30 s) <90% seen in 8/36 (22%) term and 9/28 (32%) ex-preterm infants; the ex-preterm babies desaturated more quickly (median 1 vs 3 min, p=0.002). CONCLUSIONS: Ex-preterm babies without BPD and who are at least 3 months CGA do not appear to be a particularly at-risk group for air travel, and routine preflight testing is not indicated. Feeding babies in an FiO(2) of 0.15 leads to a further fall in SpO(2), which is significant but transient.

A fatal case of cough.

Dysfunctional swallowing is an uncommon, but important cause of bronchiectasis. We describe a child with a brainstem tumor, who developed bronchiectasis caused by chronic aspiration secondary to a dysfunctional swallow. The case highlights the importance of thorough and repeated evaluation before a diagnosis of idiopathic bronchiectasis is made. If dysfunctional swallow is found further investigation to ascertain the cause is indicated.

The importance of nurse-led home visits in the assessment of children with problematic asthma.

OBJECTIVE: To evaluate and identify potentially modifiable factors in children with problematic asthma by a nurse-led assessment and home visit. DESIGN: Observational cohort study. SETTING: A tertiary paediatric respiratory centre. PATIENTS: 71 children, aged 4.5-17.5 years, with problematic asthma currently under follow-up at a tertiary respiratory centre. INTERVENTIONS: A nurse-led hospital visit followed by a home visit. MAIN OUTCOME MEASURES: Identification and attempted change of exacerbating factors so that further investigations and consideration of off-label, potentially toxic, asthma therapies were not necessary. RESULTS: Potentially modifiable factors were identified in 56 (79%) children. Many children had multiple causes for poor control. The most important were ongoing allergen exposure, 22 children (31%); passive or active smoking, 18 children (25%); medication issues including adherence, 34 children (48%); psychosocial factors, 42 families (59%). The home visit contributed valuable information to this assessment. At the home visit house dust mite avoidance measures were found to be inadequate in 84% of those sensitised; medications were not easily available for inspection or were out of date in 23%; 74% of psychology referrals were made after the home visit. In 39 children (55%) the factors identified and the interventions recommended meant that further escalation of treatment was avoided. CONCLUSIONS: Nurse-led assessments including a home visit can help identify potentially modifiable factors for poorly controlled symptoms in children with problematic asthma.