Asthma morbidity and ambient air pollution: effect modification by residential traffic-related air pollution.

BACKGROUND: Ambient air pollution has been associated with asthma-related hospital admissions and emergency department visits (hospital encounters). We hypothesized that higher individual exposure to residential traffic-related air pollutants would enhance these associations. METHODS: We studied 11,390 asthma-related hospital encounters among 7492 subjects 0-18 years of age living in Orange County, California. Ambient exposures were measured at regional air monitoring stations. Seasonal average traffic-related exposures (PM2.5, ultrafine particles, NOx, and CO) were estimated near subjects' geocoded residences for 6-month warm and cool seasonal periods, using dispersion models based on local traffic within 500 m radii. Associations were tested in case-crossover conditional logistic regression models adjusted for temperature and humidity. We assessed effect modification by seasonal residential traffic-related air pollution exposures above and below median dispersion-modeled exposures. Secondary analyses considered effect modification by traffic exposures within race/ethnicity and insurance group strata. RESULTS: Asthma morbidity was positively associated with daily ambient O3 and PM2.5 in warm seasons and with CO, NOx, and PM2.5 in cool seasons. Associations with CO, NOx, and PM2.5 were stronger among subjects living at residences with above-median traffic-related exposures, especially in cool seasons. Secondary analyses showed no consistent differences in association, and 95% confidence intervals were wide, indicating a lack of precision for estimating these highly stratified associations. CONCLUSIONS: Associations of asthma with ambient air pollution were enhanced among subjects living in homes with high traffic-related air pollution. This may be because of increased susceptibility (greater asthma severity) or increased vulnerability (meteorologic amplification of local vs. correlated ambient exposures).

Treatment with tobramycin solution for inhalation reduces hospitalizations in young CF subjects with mild lung disease.

Our objective was to study the effect of tobramycin solution for inhalation (TSI; TOBI, Chiron Corp.) on lung function decline rate in 400 young persons with cystic fibrosis (CF) and mild lung disease. Effects on hospitalization, antibiotic use, school days missed, and nutritional status also were determined. This was an open-label, randomized (stratified by sex and age group, i.e., 6-10 and 11-15 years), parallel-group, multicenter study. Routine subject management (control group) was compared to routine management plus 28 days of twice-daily TSI inhalation, followed by 28 days off the drug (TSI group) for 56 weeks. Primary efficacy endpoints included rate of lung function decline (as measured by forced expiratory volume in 1 sec; FEV(1)), hospitalization, and concomitant antibiotic use. Safety was assessed by analysis of treatment-emergent adverse events. Only 184 of 400 planned subjects were recruited and randomized (93 to the TSI group, and 91 to the control group). Enrollment was ended after 2 years because of difficult recruitment. An interim safety review showed a 2.42-fold risk of respiratory hospitalization for control group subjects (P = 0.020), and the study was terminated. Sixty-three subjects (34.2%) completed the entire study (30 in the TSI group, or 32.3%; and 33 in the control group, or 36.3%). Significantly fewer TSI subjects were hospitalized for worsening of respiratory symptoms (11.0% vs. 25.6%; P = 0.011), and fewer TSI subjects were hospitalized overall (16.5% vs. 27.8%; P = 0.065). Fewer TSI subjects received antibiotics other than the study drug (78.0% vs. 95.6%), and significantly fewer received oral antibiotics (76.9% vs. 91.1%; P = 0.009). No other safety or adverse event differences were observed. In conclusion, significant reductions in respiratory hospitalizations, concomitant antibiotic use, and a trend towards improvement in percent predicted forced expiratory flow (FEF(25-75)) provide evidence of a clinical benefit of TSI use in young persons with CF and mild lung disease. An effect on lung function decline rate could not be evaluated as planned, due to inadequate enrollment and early study termination.

Usefulness of cerebral NIRS in detecting the effects of pediatric sleep apnea.

BACKGROUND: Children with sleep apnea have increased morbidity if the sleep apnea is untreated. Polysomnography (PSG) is used to detect sleep apnea, but in children, there are technical difficulties that make the diagnosis more difficult. Cerebral near infrared spectroscopy (NIRS) has the ability to detect tissue hypoxia by measuring regional oxygen saturation (rSO2 ). We hypothesized that when used as an adjunct to PSG testing, cerebral NIRS would better detect the effects of sleep apnea in children than arterial pulse oximetry (SpO2 ). Specifically, we aimed to show that the apnea/hypopnea index (AHI) calculated with rSO2 from the NIRS would be greater than that calculated with SpO2 . METHODS: Forty-seven patients under 18 years of age who underwent PSG testing for sleep apnea were evaluated. Cerebral NIRS was utilized in addition to PSG. The AHI was calculated using SpO2 and compared to the AHI calculated using the rSO2 . A pediatric pulmonologist who was unaware of the NIRS data evaluated each patient for sleep apnea. Data are median (interquartile range). RESULTS: The median AHI(rSO2 ) was 2.4(1.2,5.1), significantly greater (P < 0.0001) than the AHI(SpO2 ) of 0.7(0.4,1.2). Four patients were diagnosed with sleep apnea; however, only one had an AHI(SpO2 ) ≥ 5, a typical threshold for the diagnosis of sleep apnea. All 4 subjects had an AHI(rSO2 ) ≥ 5 but 10 patients without sleep apnea had a value ≥5. The sensitivity and specificity for using the AHI(rSO2 ) to diagnose sleep apnea was 100% and 76.7%, respectively. CONCLUSION: Consistent with the ability of NIRS to detect tissue hypoxia, we found that the AHI calculated with rSO2 was greater than that using SpO2 . We conclude that NIRS has potential as a valuable adjunct to PSG in evaluating patients for sleep apnea and warrants further investigation for this purpose.

Novel CFTR variants identified during the first 3 years of cystic fibrosis newborn screening in California.

California uses a unique method to screen newborns for cystic fibrosis (CF) that includes gene scanning and DNA sequencing after only one California-40 cystic fibrosis transmembrane conductance regulator (CFTR) panel mutation has been identified in hypertrypsinogenemic specimens. Newborns found by sequencing to have one or more additional mutations or variants (including novel variants) in the CFTR gene are systematically followed, allowing for prospective assessment of the pathogenic potential of these variants. During the first 3 years of screening, 55 novel variants were identified. Six of these novel variants were discovered in five screen-negative participants and three were identified in multiple unrelated participants. Ten novel variants (c.2554_2555insT, p.F1107L, c.-152G>C, p.L323P, p.L32M, c.2883_2886dupGTCA, c.2349_2350insT, p.K114del, c.-602A>T, and c.2822delT) were associated with a CF phenotype (42% of participants were diagnosed at 4 to 25 months of age), whereas 26 were associated with CFTR-related metabolic syndrome to date. Associations with the remaining novel variants were confounded by the presence of other diseases or other mutations in cis or by inadequate follow-up. These findings have implications for how CF newborn screening and follow-up is conducted and will help guide which genotypes should, and which should not, be considered screen positive for CF in California and elsewhere.

Lung function measurement in the assessment of childhood asthma: recent important developments.

PURPOSE OF REVIEW: To present three clinically important developments related to the utilization of pulmonary function to objectively assess the asthmatic child. RECENT FINDINGS: The new asthma guidelines (2007) have added the forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio to the FEV1 as spirometric criteria for classifying asthma. Although a better indicator of airway obstruction, it has not clearly been shown to correlate with clinical criteria. The normal cut point for the ratio used in the guidelines of 85% for children may be too high, and compared to the lower limits of normal of 80%, could result in unnecessary treatment in some children. The bronchodilator response (BDR) phenotype reflects airway lability and has been associated with biomarkers of inflammation and responsiveness to inhaled corticosteroids as well as predicting long-term outcomes. Several studies have shown improved spirometric techniques in preschoolers as well as defining normal values in this age group. Impulse oscillometry (IOS), which is less demanding than spirometry, has been shown to identify asthmatic preschoolers in some cases better than spirometry and possibly identifying obstruction in the peripheral airways. It may also be a more useful test than spirometry in evaluating long-term drug studies. SUMMARY: In addition to the FEV1/FVC ratio to detect airway obstruction, the BDR phenotype would appear to give important additional information regarding airway lability and inflammation, and should be included as routine spirometry. IOS is a promising test to identify asthmatic preschoolers, but more studies are needed to determine exactly what it measures and what constitutes normal values.

Repeated hospital encounters for asthma in children and exposure to traffic-related air pollution near the home.

BACKGROUND: Aggregate hospital encounters for asthma (admissions or emergency department visits) have been associated with daily regional air pollution. There are fewer data on relationships between repeated hospital encounters and traffic-related air pollution near the home. OBJECTIVE: To estimate the association of local traffic-generated air pollution with repeated hospital encounters for asthma in children. METHODS: Hospital records for 2,768 children aged 0 to 18 years (697 of whom had > or = 2 encounters) were obtained for a catchment area of 2 hospitals in northern Orange County, California. Residential addresses were geocoded. A line source dispersion model was used to estimate individual seasonal exposures to local traffic-generated pollutants (nitrogen oxides and carbon monoxide) longitudinally beginning with the first hospital encounter. Recurrent proportional hazards analysis was used to estimate risk of exposure to air pollution adjusting for sex, age, health insurance, census-derived poverty, race/ethnicity, residence distance to hospital, and season. The adjustment variables and census-derived median household income were tested for effect modification. RESULTS: Adjusted hazard ratios for interquartile range increases in nitrogen oxides (4.00 ppb) and carbon monoxide (0.056 ppm) were 1.10 (95% confidence interval, 1.03-1.16) and 1.07 (1.01-1.14), respectively. Associations were strongest for girls and infants but were not significantly different from other groups. Stronger associations in children from higher-income block groups (P < .09 for trend) may have been due to more accurate data. CONCLUSIONS: Associations for repeated hospital encounters suggest that locally generated air pollution near the home affects asthma severity in children. Risk may begin during infancy and continue in later childhood, when asthma diagnoses are clearer.