Asthma Control Test and Bronchial Challenge with Exercise in Pediatric Asthma.

BACKGROUND: Poor asthma control can lead to exercise-induced bronchoconstriction (EIB), but the relationship between subjective disease control and EIB is unclear. No studies have compared asthma control test (ACT) scores of children with those of their parents regarding EIB. We assessed whether ACT scores predict the occurrence of EIB in two age groups. We also evaluated ACT scores and objective measures as explanatory variables for airway response to exercise. METHODS: Patients (71, aged <12 years; 93, aged ≥12 years) and their parents completed an ACT questionnaire separately. Current therapy, skin prick testing, and spirometry at baseline and after exercise were assessed. EIB was defined as a fall in forced expiratory volume in 1 s (FEV1) of at least 12% from baseline. Sensitivity and specificity for cut-off values of ACT scores predictive of EIB were plotted, and the area under curve (AUC) was described. RESULTS: Atopy and current therapy were similarly frequent. EIB was observed in 23.9% of children aged <12 years and in 33.3% of children aged ≥12 years. EIB occurrence in subjects previously scored as having full control (25), partial control (20-24), and no control (<20) varied according to the age group and responders. Percentages of EIB cases increased as ACT scores decreased in children aged ≥12 years alone (child ACT scores, 25: 21.9%, 20-24: 31.1%, <20: 62.5%, p = 0.017). Plots for ACT scores as predictors of EIB yielded low non-significant AUC values in children aged <12 years; in contrast, moderate AUC values emerged in children aged ≥12 years (child: 0.67, p = 0.007; parent: 0.69, p = 0.002). Sensitivity of ACT scores below 20 as a predictor of EIB was low in older children (child: 32.3%, parent: 22.6%), whereas specificity was high (child: 90.3%, parent: 93.5%). Multiple regression analysis with percent fall in FEV1 as dependent variable included FEV1/FVC%, ACT child score, and gender in the prediction model (r = 0.42, p = 0.000). CONCLUSION: ACT scores are a more effective means of excluding than confirming EIB in asthmatic patients aged ≥12 years; their predictive value decreases in younger patients. ACT scores together with lung function may help to predict airway response to exercise. New tools for pediatric asthma assessment may optimize this association.

Chronic granulomatous disease mimicking early-onset Crohn's disease with cutaneous manifestations.

BACKGROUND: Chronic granulomatous disease is a rare inherited disorder of the innate immune system. In patients with a clinical history of recurrent or persistent infections, especially infections caused by uncommon species, chronic granulomatous disease should be considered. CASE PRESENTATION: We report the case of a 5-year-old boy with a presumptive diagnosis of Crohn's disease with extraintestinal manifestations. Chronic granulomatous disease was suspected in this case after Serratia marcescens was isolated from a skin ulcer culture. Granulomas were confirmed on histology and chronic granulomatous disease was diagnosed. CONCLUSION: This case emphasizes the importance of high clinical suspicion of an alternative diagnosis of immune deficiency in patients with presumed inflammatory bowel disease and opportunistic infections, especially when disease occurs in early life.

Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency.

BACKGROUND: Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear. OBJECTIVE: We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life. METHODS: We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency. RESULTS: The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 µmol/L (normal value, <1.5 µmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 µmol/L (normal value, <0.07 µmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis. CONCLUSION: Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency.

Influence of cartilage and menisci on the sagittal slope of the tibial plateaus.

We analyzed the magnetic resonance studies of the knee in 80 subjects, 45 men and 35 women with a mean age of 38.9 years, who showed no pathological condition of the joint. Using an imaging visualization software, the sagittal longitudinal axis of the tibia was identified. The angle between this axis and a line tangent to the bone profile of the tibial plateau (bone slope) and to the superior border of the menisci (meniscal slope) were calculated. Thickness of anterior and posterior portion of menisci and underlying cartilage were also measured. The bone slope averaged 8° and 7.7° on the medial and lateral sides, respectively. The mean meniscal slope was 4.1° and 3.3° on the medial and lateral sides, respectively, with a significant difference compared with the bone slope. Menisci and underlying cartilage were significantly thicker in their posterior than their anterior portion (7.6 and 5.2 mm, respectively, in the medial compartment; 8.6 and 5.2 mm, respectively, in the lateral compartment). The presence of cartilage and menisci implies a significant decrease in the posterior tibial slope. In the lateral compartment, the greater the bone slope, the larger the difference between bone and meniscal slope, which means that a marked posterior tilt of the lateral tibial plateau is decreased by the cartilage and meniscus. These findings should be taken into account in planning surgical procedures which affect the slope of the articular tibial surface.

Molecular profiles of IgE to Phleum pratense in children with grass pollen allergy: implications for specific immunotherapy.

BACKGROUND: The so-called component-resolved immunotherapy of allergies proposes an immunization tailored to the molecular sensitization profiles of individual patients. OBJECTIVES: We sought (1) to investigate the profiles of IgE sensitization to Phleum pratense in children with grass pollen allergy and (2) to define the compatibility of these profiles with a mixture of recombinant allergenic molecules of P pratense previously proposed for specific immunotherapy. METHODS: We examined 200 children (age, 4-18 years; 126 boys) with allergic rhinitis, asthma, or both ascertained through validated questionnaires. Each child underwent skin prick testing (ALK-Abelló) and serum IgE assays (ImmunoCAP, Phadia) with 9 pollen extracts. Sera reacting against P pratense were tested for the individual molecules (rPhl p 1, rPhl p 2, rPhl p 4, nPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, and Phl p 12). Through a combinatorial approach, the IgE individual sensitization profiles were matched against an experimental allergen-specific immunotherapy (SIT) preparation containing Phl p 1, Phl p 2, Phl p 5, and Phl p 6. RESULTS: Among the 176 of 200 children with IgE sensitization to P pratense extract, 39 profiles of sensitization to the 8 allergenic molecules tested (cutoff, 0.35 kU/L) were identified. This high heterogeneity was reduced by considering only 6 or 4 P pratense molecules but not by increasing the cutoff levels of IgE positivity. The molecular profile of the experimental SIT preparation matched that of 7 (4%) of 176 patients only; the remaining 169 patients were classified in 4 mismatch categories: underpowered (29%), overpowered (32%), underpowered/overpowered (32%), and unrelated (3%). CONCLUSIONS: IgE sensitization profiles to P pratense are highly heterogeneous. Molecularly designed SIT preparations tailored to patients' needs should consider this high heterogeneity and be driven by locally performed population studies.