Evaluation of clinically and physiologically atypical asthma: If it doesn't wheeze it may still be asthma.

OBJECTIVE: Children with asthma-like symptoms may not clinically wheeze. The objectives of this study were to evaluate if children, without physician-documented wheeze, wheeze during bronchial-challenge-testing (BCT), and if measurements of O2Sat and respiratory rate during BCT improve the BCT sensitivity? METHODS: Seven hundred and twenty-four children, who were referred for suspicion of asthma, performed a BCT. Positive BCT was determined by the provocation concentration (PC) which resulted in a 20% decrease in FEV1 (PC20), (in those who were able to perform spirometry, group B), or (in those unable to perform spirometry, group A) a 50% increase in respiratory rate (PCRR), or a 5% decrease in oxygen-saturation (PCO2-Sat) or appearance of wheezing (PCwheeze). RESULTS: Five hundred and seven BCTs were positive: group A n = 89 age, median (IQR), 3 (2.5-3.7) years (17.6%), were unable to perform spirometry, and group B n = 418 age 10.7 (6.8-15.6) years (82.4%), were able to perform spirometry. Children, without physician-documented wheeze in the total population (groups A plus B), were more likely (65.5%) to have a positive BCT without wheeze compared with those with physician-documented wheeze (41.0%, P < 0.001). In group A, adding PCRR and PCO2-Sat increased BCT sensitivity by 23.6%. CONCLUSIONS: Many children in both groups did not wheeze despite reaching BCT endpoints. Children without physician-documented wheeze tended not to wheeze at BCT. This may result in clinical under-diagnosis of asthma if depending on the presence of wheeze. In young children, adding PCRR and PCO2-Sat substantially increases BCT sensitivity and may improve asthma diagnosis.

Clinical outcome in children with culture-negative acute otitis media.

BACKGROUND: Culture-negative AOM is often milder and associated with lower local/systemic inflammatory responses than culture-positive AOM. STUDY OBJECTIVES: To compare the clinical outcome of culture-negative AOM with that of culture-positive AOM children. PATIENTS AND METHODS: Children aged 3 to 35 months with AOM were enrolled in 11 double-tympanocentesis antibiotic efficacy studies documenting both bacteriologic (days 4-6 of treatment) and clinical outcome (days 11-14, end of treatment). Univariate analysis (age, gender, ethnicity, previous AOM history, and antibiotic treatment) between culture-negative and culture-positive AOM patients was performed by Student t test, ANOVA, or chi2 test. Those found to be significant were further submitted to multivariable regression analysis. RESULTS: A total of 1088 patients (mean age, 11.95 +/- 5.96 months, 209 culture-negative and 879 culture-positive AOM) were enrolled. No differences were recorded between culture-negative AOM and culture-positive AOM patients in age, gender, ethnicity and number of previous episodes. Seventy-four percent (650/879) culture-positive AOM patients achieved bacteriologic eradication within 3 to 5 days. Successful outcome (cured + improved) was recorded in 90% (189/209) culture-negative AOM patients versus 86% (758/879) in culture-positive AOM (P = 0.086). Successful clinical outcome was more frequent in culture-negative than in culture-positive AOM without bacteriologic eradication (90% vs. 67% [154/229], P < 0.001). No difference in successful clinical outcome was found between culture-negative versus culture-positive AOM patients with bacterial eradication (90% vs. 93% [604/650], P = 0.24). Overall, the inclusion of culture-negative AOM patients in the evaluation of clinical failures rates in study patients decreased the total clinical failure rate by 9%. We present a hypothetical antibiotic efficacy study enrolling 300 patients in whom 2 drugs with different bacteriologic efficacy rates (A-90% and B-60%) were used. When the culture-negative cases (5% clinical failure) enrolled increased from 50/300 (16.7%) to 150/300 (50%), the overall clinical failure rate decreased by 36% (from 17.4% to 11.2%, P = 0.08) for the less efficacious drug, while remaining unmodified for the more efficacious drug (9.6% and 8.8%, respectively). CONCLUSIONS: (1) Clinical outcome in culture-negative AOM was similar to that of culture-positive AOM with bacteriologic eradication and both were superior to that of culture-positive AOM without eradication; (2) Inclusion of culture-negative AOM patients in series aiming at antibiotic efficacy may falsely improve the clinical outcome for antibiotics with reduced ability to eradicate AOM pathogens.