Search

Club cell secretory protein (CC16) exerts anti-inflammatory functions in lung disease. We sought to determine the relation of serum CC16 deficits and genetic variants that control serum CC16 to lung function among children with cystic fibrosis (CF).We used longitudinal data from CF children (EPIC Study) with no positive cultures for Pseudomonas aeruginosa prior to enrollment. Circulating levels of CC16 and an inflammatory score (generated from CRP, SAA, calprotectin, G-CSF) were compared between participants with the lowest and highest FEVCompared with the HLF group, the LLF group had lower levels of CC16 (geometric means: 8.2 vs 6.5 ng/ml, respectively; p = 0.0002) and higher levels of the normalized inflammatory score (-0.21 vs 0.21, p = 0.0007). Participants in the lowest CC16 and highest inflammation tertile had the highest odds for having LLF (p0.0001 for comparison with participants in the highest CC16 and lowest inflammation tertile). Among seven SNVs associated with circulating CC16, the top SNV rs3741240 was associated with decline of FEVSerum CC16 deficits are strongly associated with severity of CF lung disease and their effects are additive with systemic inflammation. The rs3741240 A allele is associated with low circulating CC16 and, possibly, accelerated lung function decline in CF.

LINE-1 (long interspersed nuclear element-1) is a group of polymorphic DNA sequences in the human genome that mobilise via RNA binding proteins, reverse transcriptase and endonuclease to alter the host genome via mutational insertions, chromosomal rearrangements and reprogramming of gene expression (reviewed by Ramos et al. [1]). Full-length LINE-1 sequences encode two proteins: L1-ORF1p, a 40-kDa protein with nucleic acid binding activity; and L1-ORF2p, a 150-kDa protein with endonuclease and reverse transcriptase activities. The activity of LINE-1 is repressed in somatic tissues via DNA methylation and covalent protein modifications, and reactivated by displacement of retinoblastoma-associated proteins from the regulatory region [2]. Recent studies in our laboratory have implicated LINE-1 as a master regulator of human bronchial epithelial cell phenotypes in experimental in vitro and in vivo models [3]., In a population-based study, higher circulating levels of L1-ORF1p were associated with lower lung function levels and increased risk for airflow limitation among former smokers http://bit.ly/2ZEIjNv

CC16 (club cell secretory protein-16), a member of the secretoglobin family, is one of the most abundant proteins in normal airway secretions and has been described as a serum biomarker for obstructive lung diseases.To determine whether low CC16 is a marker for airway pathology or is implicated in the pathophysiology of progressive airway damage in these conditions.Using human data from the birth cohort of the Tucson Children's Respiratory Study, we examined the relation of circulating CC16 levels with pulmonary function and responses to bronchial methacholine challenge from childhood up to age 32 years. In wild-type and CC16We observed that Tucson Children's Respiratory Study participants in the lowest tertile of serum CC16 had significant deficits in their lung function and enhanced airway hyperresponsiveness to methacholine challenge from 11 years throughout young adult life. Similarly, CC16Our findings support clinical observations by providing evidence that lack of CC16 in the lung results in dramatically altered pulmonary function and structural alterations consistent with enhanced remodeling.

Spirometric restriction, defined as a reduced forced vital capacity (FVC) with a preserved FEVIn this longitudinal, multicohort, population-based study, we used data from the Tucson Children's Respiratory Study (TCRS), which recruited 1246 healthy infants at birth between April 1980, and October 1984, in Tucson, AZ, USA. Questionnaires were answered by the primary caregiver at enrolment, immediately after the child's birth, and multiple follow-up questionnaires were completed through childhood and adulthood. At the age of 22, 26, 32, and 36 years, lung function was measured with spirometry. At each survey, three mutually exclusive spirometric patterns were defined: (1) normal (FEVOf 1246 healthy infants included in TCRS, for the present study we included data for 652 participants who had at least one set of spirometry data, contributing up to 1668 observations. In the TCRS cohort, results from the multivariate models showed that maternal nutritional problems during pregnancy (RRR 2·48 [95% CI 1·30-4·76]; p=0·0062), being born small for gestational age (birthweight10th percentile; 3·26 [1·34-7·93]; p=0·0093), and being underweight in childhood (BMI-for-age5th percentile; 3·54 [1·35-9·26]; p=0·010) were independent predictors of spirometric restriction in adult life. Associations between being small for gestational age (p=0·0028) and underweight in childhood (p0·0001) with adult spirometric restriction were supported by the results of meta-analysis of data from all three cohorts. In the MAAS cohort, having a low lean BMI (ie,10th percentile) at age 11 years predicted adult (age 18 years) spirometric restriction (RRR 3·66 [1·48-9·02]; p=0·0048). These associations of spirometric restriction with small for gestational age, childhood underweight, and low lean BMI in childhood were verified in participants with spirometric restriction who had diminished total lung capacity, indicating that these factors specifically increase the risk of lung restriction.Poor growth and nutritional deficits in utero and throughout childhood precede and predict the development of spirometric restriction in adult life. Strategies to improve prenatal and childhood growth trajectories could help to prevent spirometric restriction and its associated morbidity and mortality burden.National Institutes of Health.

Rationale: Deficits in infant lung function—including the ratio of the time to reach peak tidal expiratory flow to the total expiratory time (tptef/te) and maximal expiratory flow at FRC (V̇maxFRC)—have been linked to increased risk for childhood asthma. Objectives: To examine the individual and combined effects of tptef/te and V̇maxFRC in infancy on risk for asthma and abnormalities of airway structure into mid-adult life. Methods: One hundred eighty participants in the Tucson Children’s Respiratory Study birth cohort had lung function measured by the chest-compression technique in infancy (mean age ± SD: 2.0 ± 1.2 mo). Active asthma was assessed in up to 12 questionnaires between ages 6 and 36 years. Spirometry and chest high-resolution computed tomographic (HRCT) imaging were completed in a subset of participants at age 26. The relations of infant tptef/te and V̇maxFRC to active asthma and airway structural abnormalities into adult life were tested in multivariable mixed models. Measurements and Main Results: After adjustment for covariates, a 1-SD decrease in infant tptef/te and V̇maxFRC was associated with a 70% (P = 0.001) and 55% (P = 0.005) increased risk of active asthma, respectively. These effects were partly independent, and two out of three infants who were in the lowest tertile for both tptef/te and V̇maxFRC developed active asthma by mid-adult life. Infant V̇maxFRC predicted reduced airflow and infant tptef/te reduced HRCT airway caliber at age 26. Conclusions: These findings underscore the long-lasting effects of the fetal origins of asthma, support independent contributions by infant tptef/te and V̇maxFRC to development of asthma, and link deficits at birth in tptef/te with HRCT-assessed structural airway abnormalities in adult life.

Study objective We evaluate the effect of implementing the out-of-hospital pediatric traumatic brain injury guidelines on outcomes in children with major traumatic brain injury. Methods The Excellence in Prehospital Injury Care for Children study is the preplanned secondary analysis of the Excellence in Prehospital Injury Care study, a multisystem, intention-to-treat study using a before-after controlled design. This subanalysis included children younger than 18 years who were transported to Level I trauma centers by participating out-of-hospital agencies between January 1, 2007, and June 30, 2015, throughout Arizona. The primary and secondary outcomes were survival to hospital discharge or admission for children with major traumatic brain injury and in 3 subgroups, defined a priori as those with moderate, severe, and critical traumatic brain injury. Outcomes in the preimplementation and postimplementation cohorts were compared with logistic regression, adjusting for risk factors and confounders. Results There were 2,801 subjects, 2,041 in preimplementation and 760 in postimplementation. The primary analysis (postimplementation versus preimplementation) yielded an adjusted odds ratio of 1.16 (95% confidence interval 0.70 to 1.92) for survival to hospital discharge and 2.41 (95% confidence interval 1.17 to 5.21) for survival to hospital admission. In the severe traumatic brain injury cohort (Regional Severity Score–Head 3 or 4), but not the moderate or critical subgroups, survival to discharge significantly improved after guideline implementation (adjusted odds ratio = 8.42; 95% confidence interval 1.01 to 100+). The improvement in survival to discharge among patients with severe traumatic brain injury who received positive-pressure ventilation did not reach significance (adjusted odds ratio = 9.13; 95% confidence interval 0.79 to 100+). Conclusion Implementation of the pediatric out-of-hospital traumatic brain injury guidelines was not associated with improved survival when the entire spectrum of severity was analyzed as a whole (moderate, severe, and critical). However, both adjusted survival to hospital admission and discharge improved in children with severe traumatic brain injury, indicating a potential severity-based interventional opportunity for guideline effectiveness. These findings support the widespread implementation of the out-of-hospital pediatric traumatic brain injury guidelines.

Background Positive serology for cytomegalovirus (CMV) has been associated with all-cause mortality risk but its role in COPD mortality is unknown. The objective of the present study was to assess the relationship between CMV serology and COPD mortality. Methods We analysed data from 806 participants in the Tucson Epidemiological Study of Airway Obstructive Disease who, at enrolment, were aged 28–70 years and had completed lung function tests. We tested CMV serology in sera from enrolment and defined “high CMV serology” as being in the highest tertile. Vital status, date and cause of death were assessed through death certificates and/or linkage with the National Death Index up to January 2017. The association of CMV serology with all-cause and cause-specific mortality risk was tested in Cox models adjusted for age, sex, level of education, body mass index, smoking status and pack-years. Results High CMV serology was marginally associated with all-cause mortality (p=0.071) but the effect was inversely dependent on age, with the association being much stronger among participants, Using a 45-year longitudinal population-based cohort, it was demonstrated for the first time that high CMV serology predicts COPD mortality risk, particularly in younger subjects, identifying a novel and early risk factor for COPD mortality http://bit.ly/32odP0Q

Alcohol intake has been associated with lung function levels inconsistently in cross-sectional studies. The goal of our study was to determine whether longitudinally-assessed light-to-moderate alcohol intake is associated with levels and decline of lung function. We examined data from 1,333 adult participants in the population-based Tucson Epidemiological Study of Airway Obstructive Disease. Alcohol intake was assessed at four surveys between 1972 and 1992. Subjects who completed at least two surveys were classified into longitudinal drinking categories (“never”, “inconsistent”, or “persistent drinker”). Spirometric lung function was measured in up to 11 surveys between 1972 and 1992. Random coefficient models were used to test for differences in lung function by drinking categories. After adjustment for sex, age, height, education, BMI categories, smoking status, and pack-years, as compared to never drinkers, persistent drinkers had higher FVC (coefficient: 157 ml, p

Study objective Survival is significantly reduced by either hypotension or hypoxia during the out-of-hospital management of major traumatic brain injury. However, only a handful of small studies have investigated the influence of the combination of both hypotension and hypoxia occurring together. In patients with major traumatic brain injury, we evaluate the associations between mortality and out-of-hospital hypotension and hypoxia separately and in combination. Methods All moderate or severe traumatic brain injury cases in the preimplementation cohort of the Excellence in Prehospital Injury Care study (a statewide, before/after, controlled study of the effect of implementing the out-of-hospital traumatic brain injury treatment guidelines) from January 1, 2007, to March 31, 2014, were evaluated (exclusions: 200 mm Hg). The relationship between mortality and hypotension (systolic blood pressure Results Among the 13,151 patients who met inclusion criteria (median age 45 years; 68.6% men), 11,545 (87.8%) had neither hypotension nor hypoxia, 604 (4.6%) had hypotension only, 790 (6.0%) had hypoxia only, and 212 (1.6%) had both hypotension and hypoxia. Mortality for the 4 study cohorts was 5.6%, 20.7%, 28.1%, and 43.9%, respectively. The crude and adjusted odds ratios for death within the cohorts, using the patients with neither hypotension nor hypoxia as the reference, were 4.4 and 2.5, 6.6 and 3.0, and 13.2 and 6.1, respectively. Evaluation for an interaction between hypotension and hypoxia revealed that the effects were additive on the log odds of death. Conclusion In this statewide analysis of major traumatic brain injury, combined out-of-hospital hypotension and hypoxia were associated with significantly increased mortality. This effect on survival persisted even after controlling for multiple potential confounders. In fact, the adjusted odds of death for patients with both hypotension and hypoxia were more than 2 times greater than for those with either hypotension or hypoxia alone. These findings seem supportive of the emphasis on aggressive prevention and treatment of hypotension and hypoxia reflected in the current emergency medical services traumatic brain injury treatment guidelines but clearly reveal the need for further study to determine their influence on outcome.

Background: Positive serology for cytomegalovirus (CMV) has been associated with all-cause mortality risk in previous studies. Aims: We sought to determine the relation of CMV serology to COPD mortality. Methods: We analyzed data from 806 participants in the TESAOD cohort who at enrollment in 1972 were aged 28–70 yrs and completed lung function tests. CMV serology in serum samples from enrollment was categorized as low, medium, and high tertiles. Date and cause of death were assessed through death certificates and linkage to the National Death Index up to January 2017. The association of CMV serology to all-cause and cause-specific mortality was tested in Cox models adjusted for age, sex, level of education, BMI, smoking status, and pack-years. Results: CMV serology was associated with subsequent all-cause mortality, but the effect was strongly dependent on age at enrollment. Among subjects Conclusions: High CMV serology is a novel and potentially modifiable risk factor for COPD mortality.

Background The World Health Organization has identified obesity as one of the most visible and neglected public health problems worldwide. Meta-analytic studies suggest that insufficient sleep increases the risk of developing obesity and related serious medical conditions. Unfortunately, the nationwide average sleep duration has steadily declined over the last two decades with 25% of U.S. adults reporting insufficient sleep. Stress is also an important indirect factor in obesity, and chronic stress and laboratory-induced stress negatively impact sleep. Despite what we know from basic sciences about (a) stress and sleep and (b) sleep and obesity, we know very little about how these factors actually manifest in a natural environment. The Assessing Daily Activity Patterns Through Occupational Transitions (ADAPT) study tests whether sleep disruption plays a key role in the development of obesity for individuals exposed to involuntary job loss, a life event that is often stressful and disrupting to an individual’s daily routine. Methods This is an 18-month closed, cohort research design examining social rhythms, sleep, dietary intake, energy expenditure, waist circumference, and weight gain over 18 months in individuals who have sustained involuntary job loss. Approximately 332 participants who lost their job within the last 3 months are recruited from flyers within the Arizona Department of Economic Security (AZDES) Unemployment Insurance Administration application packets and other related postings. Multivariate growth curve modeling will be used to investigate the temporal precedence of changes in social rhythms, sleep, and weight gain. Discussion It is hypothesized that: (1) unemployed individuals with less consistent social rhythms and worse sleep will have steeper weight gain trajectories over 18 months than unemployed individuals with stable social rhythms and better sleep; (2) disrupted sleep will mediate the relationship between social rhythm disruption and weight gain; and (3) reemployment will be associated with a reversal in the negative trajectories outlined above. Positive findings will provide support for the development of obesity prevention campaigns targeting sleep and social rhythms in an accessible subgroup of vulnerable individuals.

Background Hospitalization of patients with chronic obstructive pulmonary disease creates a huge healthcare burden. Positive airway pressure therapy is sometimes used in patients with chronic obstructive pulmonary disease, but the possible impact on hospitalization risk remains controversial. We studied the hospitalization risk of patients with chronic obstructive pulmonary disease before and after initiation of various positive airway pressure therapies in a "real-world" bioinformatics study. Methods We performed a retrospective analysis of administrative claims data of hospitalizations in patients with chronic obstructive pulmonary disease who received or did not receive positive airway pressure therapy: continuous positive airway pressure, bilevel positive airway pressure, and noninvasive positive pressure ventilation using a home ventilator. Results The majority of 1,881,652 patients with chronic obstructive pulmonary disease (92.5%) were not receiving any form of positive airway pressure therapy. Prescription of bilevel positive airway pressure (1.5%), continuous positive airway pressure (5.6%), and noninvasive positive pressure ventilation ( Conclusion Initiation of positive airway pressure therapy was associated with reduction in hospitalization among patients with chronic obstructive pulmonary disease, but the causality needs to be determined by randomized controlled trials.

Traumatic brain injury (TBI) exacts a great toll on society. Fortunately, there is growing evidence that the management of TBI in the early minutes after injury may significantly reduce morbidity and mortality. In response, evidence-based prehospital and in-hospital TBI treatment guidelines have been established by authoritative bodies. However, no large studies have yet evaluated the effectiveness of implementing these guidelines in the prehospital setting. This article describes the background, design, implementation, emergency medical services (EMS) treatment protocols, and statistical analysis of a prospective, controlled (before/after), statewide study designed to evaluate the effect of implementing the EMS TBI guidelines-the Excellence in Prehospital Injury Care (EPIC) study (NIH/NINDS R01NS071049, "EPIC"; and 3R01NS071049-S1, "EPIC4Kids"). The specific aim of the study is to test the hypothesis that statewide implementation of the international adult and pediatric EMS TBI guidelines will significantly reduce mortality and improve nonmortality outcomes in patients with moderate or severe TBI. Furthermore, it will specifically evaluate the effect of guideline implementation on outcomes in the subgroup of patients who are intubated in the field. Over the course of the entire study (~9 years), it is estimated that approximately 25,000 patients will be enrolled.

IMPORTANCE: Traumatic brain injury (TBI) is a massive public health problem. While evidence-based guidelines directing the prehospital treatment of TBI have been promulgated, to our knowledge, no studies have assessed their association with survival. OBJECTIVE: To evaluate the association of implementing the nationally vetted, evidence-based, prehospital treatment guidelines with outcomes in moderate, severe, and critical TBI. DESIGN, SETTING, AND PARTICIPANTS: The Excellence in Prehospital Injury Care (EPIC) Study included more than 130 emergency medical services systems/agencies throughout Arizona. This was a statewide, multisystem, intention-to-treat study using a before/after controlled design with patients with moderate to critically severe TBI (US Centers for Disease Control and Prevention Barell Matrix-Type 1 and/or Abbreviated Injury Scale Head region severity ≥3) transported to trauma centers between January 1, 2007, and June 30, 2015. Data were analyzed between October 25, 2017, and February 22, 2019. INTERVENTIONS: Implementation of the prehospital TBI guidelines emphasizing avoidance/treatment of hypoxia, prevention/correction of hyperventilation, and avoidance/treatment of hypotension. MAIN OUTCOMES AND MEASURES: Primary: survival to hospital discharge; secondary: survival to hospital admission. RESULTS: Of the included patients, the median age was 45 years, 14 666 (67.1%) were men, 7181 (32.9%) were women; 16 408 (75.1% ) were white, 1400 (6.4%) were Native American, 743 (3.4% ) were Black, 237 (1.1%) were Asian, and 2791 (12.8%) were other race/ethnicity. Of the included patients, 21 852 met inclusion criteria for analysis (preimplementation phase [P1]: 15 228; postimplementation [P3]: 6624). The primary analysis (P3 vs P1) revealed an adjusted odds ratio (aOR) of 1.06 (95% CI, 0.93-1.21; P = .40) for survival to hospital discharge. The aOR was 1.70 (95% CI, 1.38-2.09; P

Purpose: To describe change in corneal astigmatism in infants and children of a Native American tribe with a high prevalence of astigmatism.Longitudinal measurements of corneal astigmatism were obtained in 960 Tohono O'odham children aged 6 months to8 years. Change in corneal astigmatism (magnitude (clinical notation), J0, J45) across age in children with high astigmatism (≥2 diopter (D) corneal astigmatism) or low/no astigmatism (2 D corneal astigmatism) at their baseline measurement was assessed.Regression analyses indicated that early in development (6 months to3 years), astigmatism magnitude decreased in the high astigmatism group (0.37 D/year) and remained stable in the low/no astigmatism group. In later development (3 to8 years), astigmatism decreased in the high (0.11 D/year) and low/no astigmatism groups (0.03 D/year). In 52 children who had data at all three of the youngest ages (6 months to1 year, 1 to2 years, 2 to3 years) astigmatism decreased after infancy in those with high astigmatism (p = 0.021), and then remained stable from age 1-2 years, whereas astigmatism was stable from infancy through age 1 year and increased from age 1-2 years in the low/no astigmatism group (p = 0.026). J0 results were similar, but results on J45 yielded no significant effects.The greatest change occurred in highly astigmatic infants and toddlers (0.37 D/year). By age 3 years, change was minimal and not clinically significant. Changes observed were due primarily to change in the J0 component of astigmatism.

Claudio Sorino,1,2 Salvatore Battaglia,1 Nicola Scichilone,1 Claudio Pedone,3 Raffaele Antonelli-Incalzi,3 Duane Sherrill,4 Vincenzo Bellia11Biomedical Department of Internal and Specialist Medicine, Section of Pulmonology, University of Palermo, Italy; 2Division of Pulmonology, S Anna Hospital, Como, Italy; 3Chair of Geriatrics, University Campus Bio-Medico, Roma, Italy; 4Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USABackground: The choice between lower limit of normal or fixed value of forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC) < 0.70 as the criterion for confirming airway obstruction is an open issue. In this study, we compared the criteria of lower limit of normal and fixed FEV1/FVC for diagnosis of airway obstruction, with a focus on healthy elderly people.Methods: We selected 367 healthy nonsmoking subjects aged 65–93 years from 1971 participants in the population-based SARA (Salute Respiratoria nell’Anziano, Italian for “Respiratory Health in the Elderly”) study, analyzed their spirometric data, and tested the relationship between spirometric indices and anthropometric variables. The lower limit of normal for FEV1/FVC was calculated as the fifth percentile of the normal distribution for selected subjects.Results: While FEV1 and FVC decreased significantly with aging, the relationship between FEV1/FVC and age was not statistically significant in men or women. The lower limit of normal for FEV1/FVC was 0.65 in men and 0.67 in women. Fifty-five participants (15%) had FEV1/FVC < 0.70 and would have been inappropriately classified as obstructed according to the Global Initiative for Obstructive Lung Disease, American Thoracic Society/European Respiratory Society, and Canadian guidelines on chronic obstructive pulmonary disease. By applying different FEV1/FVC thresholds for the different age groups, as previously proposed in the literature, (0.70 for 80 years) the percentage of patients classified as obstructed decreased to 6%. No subjects older than 80 years had an FEV1/FVC < 0.60.Conclusion: The present results confirm the inadequacy of FEV1/FVC < 0.70 as a diagnostic criterion for airway obstruction after the age of 65 years. FEV1/FVC < 0.65 and

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a leading cause of hospitalizations in the United States and the major cost driver of COPD. This study determined the national inpatient burden of AECOPD and assessed the association of co-morbidities and hospital characteristics with inpatient costs and mortality. Discharge records from the Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample for 2006 was utilized. Outcomes of costs and mortality were assessed for AECOPD hospitalizations in cases ≥40 years of age. Multivariate regression analyses using a generalized linear model framework were conducted to determine predictors of inpatient costs and mortality controlling for patient demographics, primary payer, co-morbidity index, length of stay, hospital region, mechanical ventilation, and admission period. Overall, 1,254,703 hospitalizations for AECOPD were observed with mean costs of $9545(±12,700) and total costs of $11.9 billion. In-hospital mortality was 4.3% (N = 53,748). Discharges averaged 70.6 (±11.9) years of age. The majority were female (52.8%) and of white race (83.6% of reported race). Several co-morbidities were signifi cantly associated with both costs and mortality ( p < 0.001): acute myocardial infarction; congestive heart failure; cerebrovascular disease; lung cancer; cardiac arrhythmias; pulmonary circulation disorders; and weight loss. Signifi cantly higher costs ( p < 0.001) were associated with large and urban hospitals. The importance of co-morbidities in AECOPD is indicated in their association with prognosis and inpatient costs. Future research should determine if better management of these conditions can favorably impact the COPD disease burden.

Familial aggregation of specific response to allergens and asthma adjusted for age and sensitization to multiple allergens was assessed in two large population cohorts. Allergen skin prick tests (SPTs) were administered to 1151 families in the Tucson Children’s Respiratory Study (CRS) and 435 families in the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD). Sensitization was defined by wheal size ≥ 3 mm; physician-diagnosed asthma at age ≥ 8 years was based on questionnaires. Using S.A.G.E. 6.1 software ASSOC and FCOR, familial correlations of crude and adjusted phenotypes were evaluated. Crude estimates of parent-offspring (P-O) and sibling correlations were statistically significant for most allergens, ranging from 0.03 to 0.29. After adjusting for age of assessment and “other atopy” (SPT-positive response to additional allergens), correlations were reduced by14–71%. Sibling correlations for specific response to allergens were consistently higher than P-O correlations, but this difference was significant only for dust mite and weed mix in the TESAOD population. Familial correlation for atopic status (any positive SPTs versus none) tended to be higher than for specific allergens. Asthma, with and without adjustment, showed greater familial correlation than either specific or general SPT response and significantly higher sibling correlation in TESAOD than in CRS, probably due to the older age of the siblings and the longer period of ascertainment. In conclusion, significant familial aggregation of specific response to allergen after adjustment for other atopy appears to reflect a genetic propensity toward atopy, dependent on shared familial exposures. Results also suggest that inheritance of asthma is independent of atopic sensitization.

To determine the impact of lower amounts of childhood sleep assessed by polysomnogram on development of obesity, being anxious or depressed, or having learning problems 5 years later.Prospective cohort.Subjects were 304 community participants from the Tucson Children's Assessment of Sleep Apnea study, aged 6-12 years old at baseline.Children were classified according to baseline sleep as those who slept ≥ 9 h/night, those who slept7.5 to9 h/night, and those who slept ≤ 7.5 h/night. Odds of overweight/obese (≥ 85(th) BMI percentile), obese (≥ 95(th) BMI percentile), anxious or depressed, and learning problems at follow-up were assessed according to baseline sleep categories. Children who slept ≤ 7.5 h/night had higher odds of being obese (OR = 3.3, P0.05) at follow-up than children who slept ≥ 9 h/night. Borderline significance for overweight/obese (OR = 2.2, P0.1), anxious or depressed (OR = 3.3, P0.1), and having learning problems (OR = 11.1, P0.1) were seen for children who slept ≤ 7.5 h/night as compared to those who slept ≥ 9 h/night. A mean increase in BMI of 1.7 kg/m(2) (P = 0.01) over the 5 years of follow-up was seen for children who slept ≤ 7.5 h/night compared to those who slept ≥ 9 h/night. These relationships did not differ between Hispanic and Caucasian children.Children with reduced amounts of sleep (≤ 7.5 h/night) had an increased risk for higher body weight in early adolescence. Similarly, children who slept ≤ 7.5 h/night had higher risk of being anxious or depressed or having learning problems in early adolescence.

Rationale Several studies have reported associations between indicators of birth size and postnatal growth rates with levels of pulmonary function achieved as adults. The objective of this study was to determine if levels and/or rates of weight gain, measured in early life (birth-6 years), are associated with FVC or FEV1 levels achieved in young adulthood and if these associations differ by early childhood wheezing phenotypes. Methods We used data from participants in the Tucson Children's Respiratory Study (CRS), a prospective birth cohort study. Weight was measured quarterly up to age 3 years and again at age 6 years. Pulmonary function was assessed at ages 16 and 22. Mean weight and slope of weight growth between 3 and 6 years were estimated using standardized residuals. Longitudinal models were used to determine predictors of FVC and FEV1 at ages 16 and 22 years. Results There were 127 non-Hispanic white subjects that had at least four weight measures and one or more pulmonary function measures as young adults. After adjusting for sex, height, and age, the standardized slope of weight growth (between 3 and 6 years) was positively associated with higher levels of FVC at age 16 and 22 years (P = 0.0001) among subjects who did not have preschool wheezing. However, this association was completely absent among subjects who had wheezing lower respiratory tract illnesses in the first 3 years of life. Similar trends were found for FEV1. Conclusion The rate of weight gain between 3 and 6 years is significantly positively related to adult FVC and FEV1 and this association is modified by early wheezy phenotypes. Pediatr. Pulmonol. 2011; 46:956–963. © 2011 Wiley-Liss, Inc.

Purpose: To evaluate and compare the drug–drug interaction (DDI) knowledge of pharmacy, medical, and nurse practitioner (NP) students who are beginning supervised clinical practice. Data sources: This study utilized a prospective evaluation of DDI knowledge among healthcare professional students who were currently enrolled in their final didactic year at the University of Arizona Colleges of Medicine, Pharmacy, or Nursing's NP program. Students were asked to assess 15 drug pairs and to select an appropriate management strategy for each pair. The primary outcome measure was the ability to correctly categorize each drug pair into one of the five management responses. The secondary outcome measure was the number of clinically significant DDIs recognized. Conclusions: Pharmacy students demonstrated significantly better knowledge than medical and NP students with respect to identifying and selecting management strategies for possible DDIs. However, there is much room for improvement for all groups. Implications for practice: An increase in curricular content that focuses on DDIs has the potential to better prepare medical, pharmacy, and NP students for practice situations involving DDI alerts, and to increase the quality of patient care.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited disease that causes structural and functional abnormalities of the right ventricle (RV). The presence of late potentials as assessed by the signal-averaged electrocardiogram (SAECG) is a minor task force criterion.The purpose of this study was to examine the diagnostic and clinical value of the SAECG in a large population of genotyped ARVC/D probands.We compared the SAECGs of 87 ARVC/D probands (age 37 ± 13 years, 47 males) diagnosed as affected or borderline by task force criteria without using the SAECG criterion with 103 control subjects. The association of SAECG abnormalities was also correlated with clinical presentation, surface ECG, ventricular tachycardia (VT) inducibility at electrophysiologic testing, implantable cardioverter-defibrillator therapy for VT, and RV abnormalities as assessed by cardiac magnetic resonance imaging (cMRI).Compared with controls, all three components of the SAECG were highly associated with the diagnosis of ARVC/D (P.001). They include the filtered QRS duration (97.8 ± 8.7 ms vs 119.6 ± 23.8 ms), low-amplitude signal (24.4 ± 9.2 ms vs 46.2 ± 23.7 ms), and root mean square amplitude of the last 40 ms of the QRS (50.4 ± 26.9 μV vs 27.9 ± 36.3 μV). The sensitivity of using SAECG for diagnosis of ARVC/D was increased from 47% using the established 2 of 3 criteria (i.e., late potentials) to 69% by using a modified criterion of any 1 of 3 criteria, while maintaining a high specificity of 95%. Abnormal SAECG as defined by this modified criterion was associated with a dilated RV volume and decreased RV ejection fraction detected by cMRI (P.05). SAECG abnormalities did not vary with clinical presentation or reliably predict spontaneous or inducible VT and had limited correlation with ECG findings.Using 1 of 3 SAECG criteria contributed to increased sensitivity and specificity for the diagnosis of ARVC/D. This finding is incorporated in the recent modification of the task force criteria.

Background Recent studies have suggested that a restrictive pattern assessed with a single spirometric test is associated with increased morbidity and mortality. This study was undertaken to determine demographic, clinical and mortality profiles of subjects with either a recurrent or an inconsistent restrictive spirometric pattern assessed prospectively. Methods Data from 2048 adult participants in the population-based TESAOD study were analysed. Normal (forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio ≥70% and FVC ≥80% predicted), restrictive (FEV1/FVC ≥70% and FVC

Background The treatment of Nocardia species found in the sputum of cystic fibrosis patients is of unknown value. Methods We conducted a retrospective analysis of the impact of directed oral antibiotic therapy against Nocardia spp. isolated from the sputum of 17 cystic fibrosis patients over a 10-year period. Pulmonary Function Tests were used as the clinical indicator of the disease state and the data were analyzed by general linear mixed model statistics with univariate analysis. Results Pulmonary Function Test values of all patients studied showed no significant difference before, during, or after the antibiotic treatment period. Treatment groups did not differ from non-treatment groups. This held true for Forced Expiratory Volume over 1 s and Functional Vital Capacity analysis. In addition, individual patient analysis did not reveal any trends or outliers. Conclusions Oral antibiotic therapy of cystic fibrosis patients colonized with Nocardia does not appear to affect clinical outcome. This suggests that deferring therapy may be an acceptable alternative and justifies conducting a future placebo controlled trial. In addition, this study model may be useful in analyzing the effect of therapy on other rare and difficult organisms, such as fungi and mycobacteria in the cystic fibrosis population.

The objective of this study was to assess tracheobronchial protease inhibitor concentrations longitudinally and determine whether initial concentrations predict subsequent lung injury and mortality in intubated burn victims. Tracheobronchial suction fluid was collected every 2 hours for 36 hours. Alpha-1-antitrypsin (AAT), secretory leukocyte peptidase inhibitor (SLPI), alpha-2-macroglobulin (A2M), and cell and differential counts were assayed. Partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FIO2) and peak airway pressure (PAP) were recorded for 72 hours. Standard statistics were used to evaluate cross-sectional relationships; random coefficient (mixed) models were used to evaluate temporal trends in marker concentrations and relation to clinical outcomes. Among 29 patients, 24 (83%) developed hypoxemia (PaO2/FIO2 35% TBSA burn (P = .010 and .033, respectively), when compared with patients with less severe burns. However, patients with increased A2M in combination with >35% TBSA burn had a 6-fold (95% CI: 1.8–20) increased relative risk of death. Tracheobronchial AAT and A2M levels were significantly lower in patients with more severe burns and increased over time. Initial SLPI levels predicted subsequent PAP. Increased early A2M in combination with extensive burn predicted early mortality.

Background: Previous studies on the relationship of chronic bronchitis to incident airflow limitation and all-cause mortality have provided conflicting results, with positive findings reported mainly by studies that included populations of young adults. This study sought to determine whether having chronic cough and sputum production in the absence of airflow limitation is associated with onset of airflow limitation, all-cause mortality and serum levels of C-reactive protein (CRP) and interleukin-8 (IL-8), and whether subjects’ age influences these relationships. Methods: 1412 participants in the long-term Tucson Epidemiological Study of Airway Obstructive Disease who at enrolment (1972–1973) were 21–80 years old and had FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ⩾70% and no asthma were identified. Chronic bronchitis was defined as cough and phlegm production on most days for ⩾3 months in two or more consecutive years. Incidence of airflow limitation was defined as the first follow-up survey with FEV1/FVC

Study Objectives: This study analyzed the association between the Respiratory Disturbance Index (RDI) and two behavior measures, the Conners' Parent Rating Scale (CPRS-R) and the Child Behavior Checklist (CBCL) in school- aged children to determine whether there is an optimal threshold of Sleep-disordered Breathing (SDB) associated with in- creased risk of behavior problems. Methods: The Tucson Children's Assessment of Sleep Apnea Study (TuCASA) is an observational cohort study of 6-11 year old Caucasian and Hispanic children designed to assess the anatomic, physiologic and neurocognitive correlates of SDB. 403 children with both polysomnography (PSG) and behavioral data were included in this analysis. Three defini- tions of SDB were used: RDI independent of oxygen desaturation (RDI0), RDI with 2% oxygen desaturation (RDI2) and RDI with 3% oxygen desaturation (RDI3). T-scored behavioral data were dichotomized at a cutoff point of 65, a score in- dicative of moderate to severe clinical impairment. Logistic regression was used to access the risk associated with SDB. Results: The analyses conducted using three different definitions of RDI suggest that the likelihood of having a clinically significant CPRS-R or CBCL subscale score was not necessarily progressive or linear across RDI categories. Cutoff points and prevalences for each definition of RDI proposed to be indicators of clinically significant SDB were RDI0 � 7 (19.38%), RDI2 � 2 (29.38%) and RDI3 � 0.5 (23.96%) events per hour of sleep. Behaviors such as CPRS oppositional, social problems, psychosomatic and CBCL somatic complaints, social problems and aggressive behaviors were found to be significantly associated with SDB. Conclusions: This analysis found an increased risk of behavior problems such as somatic complaints, oppositional or ag- gressive behaviors and social problems associated with sleep-disordered breathing in school-aged children. RDI cut points for three definitions of SDB are proposed: 7 for RDI0, 2 for RDI2, and 0.5 for RDI3 respectively.

Background It is well known that homozygous deficiency of α 1 -antitrypsin, PiZZ, is associated with an increased risk of emphysema. However, studies evaluating associations between the heterozygous form PiMZ with emphysema and impaired lung function have provided conflicting results. Study objective The goal of this study was to determine if the phenotype PiMZ is associated with an accelerated decline in diffusing capacity of the lung for carbon monoxide (D lco ). Design and methods The Tucson Epidemiologic Study of Airway Obstructive Disease is a prospective, population-based cohort study initiated in 1972. Participants completed standardized questionnaires in up to 12 periodic surveys and D lco assessments in up to 4 surveys. Random-effects models were used to determine the effects of α 1 -antitrypsin phenotypes on percentage of predicted (% predicted) D lco levels among 1,075 subjects ≥ 18 years old. Results % predicted D lco declined more rapidly in subjects who smoked compared to nonsmoking subjects. Additionally, in smokers, the PiMZ phenotype was associated with borderline % predicted D lco deficits at age 40 years (8.6%; p = 0.075) and significant % predicted D lco deficits at age 60 years (15.2%; p = 0.001) and 80 years (21.9%; p = 0.003), as compared with the PiMM phenotype. Conclusions D lco may be a more sensitive indicator of the long-term effects of intermediate levels of α 1 -antitrypsin on lung function especially in subjects who smoke.

Although smoke inhalation injury victims frequently develop severe hypoxemia and are at increased risk of acute respiratory distress syndrome (ARDS), no early prognostic tests are currently available. The objectives were to determine early longitudinal changes in tracheobronchial fluid inflammatory markers and assess the value of initial concentrations as predictors of subsequent lung injury. Partial pressure of arterial oxygen (Pao2) and the fraction of inspired oxygen (Fio2) were recorded approximately every 6 hours from intubated smoke inhalation victims admitted to a regional burn center. Tracheobronchial suction fluid was collected every 2 hours and assayed for interleukins (IL-1beta, -8, and -10), tumor necrosis factor-alpha, transforming growth factor-beta1, soluble Fas ligand (sFasL), and complement factor 5a. Temporal trends in marker concentrations during 36 hours and the relations between initial concentrations and lowest Pao2/Fio2 or ARDS within 72 hours were assessed using random coefficients modeling and cross-sectional analysis. In 21 subjects with tracheobronchial samples collected within 6.5 hours of intubation, 14 (66.7%) developed acute hypoxemia (Pao2/Fio2or =200) within 72 hours of exposure and nine (42.9%) developed ARDS, as defined by the American-European consensus conference on ARDS. IL-8 increased sharply in the first 6.5 hours postexposure (P.001), and IL-1beta in the first 6.1 hours (P.001). No significant temporal trends in IL-10, tumor necrosis factor-alpha, transforming growth factor-beta1, sFasL, or complement factor 5a were found. Only initial IL-8 was associated with increased Pao2/Fio2 (P = .013) and with a minimum Pao2/Fio2200 (P = .042) during 72 hours. In smoke inhalation victims, tracheobronchial IL-1beta and IL-8 increase rapidly and high initial IL-8 may predict improved oxygenation.

Studies evaluating the safety of salmeterol are inconclusive, which might be the result from not taking into account the impact of concomitant inhaled corticosteroids (ICS).To study whether salmeterol use with and without concomitant ICS, respectively, was associated with an increased risk of asthma-related hospitalizations among patients with asthma.A case-control study nested within a cohort of patients with asthma, identified in the year 2000, over a 2-year period was conducted. Cases were subjects who had a first-time hospitalization for asthma in the year 2001, and were matched with up to five controls by age (+/- 5 years), sex, and number of asthma-related outpatient visits.Hospitalizations and medication use were extracted from the MEDSTAT's MarketScan database.There were 333 cases of asthma-related hospitalizations and 1607 matched control subjects. Any use of salmeterol with concomitant ICS use during the prior year was associated with a 32% risk reduction for being hospitalized due to asthma (OR = 0.68; 95% CI = 0.48, 0.96). In the presence of concomitant ICS use, patients who either used salmeterol currently or used seven or more canisters of salmeterol during the prior year had 46% (OR = 0.54, 95% CI = 0.32, 0.92), and 59% (OR = 0.41, 95% CI = 0.21, 0.79) reductions in the risk of hospital admissions for asthma, respectively.Though indirect measure of asthma severity was adjusted during the analyses, the lack of information on lung function might result in a selection bias. Additionally, only a small sample size of patients was found to use salmeterol without concomitant ICS use, and this introduced the issue of lack of power.Use of salmeterol in conjunction with ICS is associated with a decreased risk of hospital admission for asthma.

Study Objective:Subjective and objective assessments of sleep may be discrepant due to sleep misperception and measurement effects, the latter of which may change the quality and quantity of a pers...

This study was performed to determine whether there is a protective association between participation in vigorous or vigorous/moderately vigorous physical activity and the prevalence of sleep-disordered breathing (SDB). Polysomnographic and questionnaire data from the baseline examination of 4,275 participants in the Sleep Heart Health Study (SHHS) were analyzed in relation to information on amount of physical activity and other potentially relevant factors collected from five SHHS parent cohorts (Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, Strong Heart Study, and Tucson Epidemiologic Study of Airways Obstructive Diseases). Logistic regression models were fitted to determine if amount and strenuousness of physical activity was associated with the presence of SDB. At least 3 h per week of vigorous physical activity reduced the odds of SDB, defined as a respiratory disturbance index (RDI) of at least 15 apneas/hypopneas per hour (Adjusted OR, 0.68; 95%CI, 0.51-0.91). A qualitatively similar but slightly weaker association was observed when SDB was defined as a RDIor = 10 per hour (Adjusted OR, 0.81; 95%CI, 0.64-1.02). These findings remained after adjustment for sleepiness and restricting analyses to participants with good health. Three or more hours of moderately vigorous or vigorous physical activity also appeared to confer some protection against SDB, but these associations were weaker. Gender- and obesity-stratified analyses suggested that the protective association between physical activity and SDB occurred primarily in men and those who were obese. A program of regular vigorous physical activity of at least 3 h per week may be a useful adjunctive treatment modality for SDB, but this association needs confirmation with a prospective clinical trial.

PURPOSE To assess longitudinal change in refractive, keratometric, and internal astigmatism in a sample of students from a population with a high prevalence of with-the-rule (WTR) astigmatism and to determine the optical origins of changes in refractive astigmatism. METHODS A retrospective analysis of longitudinal measurements of right eye refractive and keratometric astigmatism in Tohono O'odham Native American children was conducted. Changes in refractive and keratometric astigmatism per year were compared in a younger cohort (n = 1594, 3 to

Research comparing parental report of sleep times to objectively obtained polysomnographic evidence of sleep times in schoolchildren is lacking. This report compares habitual sleep time and objectively recorded sleep time and sleep latency with parental reports of sleep time immediately after a night of polysomnography in elementary schoolchildren. Unattended home polysomnograms (PSG) were obtained from 480 children. On the night of the PSG, a parent was asked to complete a Sleep Habits Questionnaire, which inquired about the habitual total sleep time (HABTST) and habitual sleep onset latency (HABSOL) of his/her child on both school days and nonschool days. On the morning after the PSG, the parent was asked to estimate the total sleep time (ESTTST) and sleep onset latency (ESTSOL) of his/her child on the night of the recording. Comparisons were made to actual total sleep time (PSGTST) and sleep latency (PSGSOL) on the PSG. The sample was comprised of 50% girls, 42.3% Hispanic, and 53% aged 6–8 years. The mean HABTST, ESTTST, and PSGTST were 578, 547, and 480 min, respectively. HABTST was greater than both ESTST and PSGTST (p

Summary Background Recurrent cough can be a clinical manifestation of rhinitis. However, it remains unclear if the association between rhinitis and recurrent cough among children is independent of asthma. Objective The aim of the present study was to determine, in a large longitudinal cohort, whether rhinitis is significantly associated with recurrent cough alone, wheezing alone, or the combination of both symptoms during childhood. Methods We investigated determinants of recurrent cough, with or without wheezing, using longitudinal data from the Tucson Children's Respiratory Study. Among the 1246 subjects originally enrolled, 1024 children completed at least one questionnaire between the ages of 6 and 18 years and were included in the present study. In any survey, wheezing was defined as at least one wheezing episode during the past year and recurrent cough as two or more coughing episodes lasting at least 1 week without a cold during the past year. Generalized estimating equations were used to determine significant risk factors. Results After adjusting for sex, skin test reactivity and parental asthma, both rhinitis (OR=2.47 CI=1.84, 3.30) and sinusitis (OR=1.54 CI=1.11, 2.14) were associated with an increased risk of recurrent cough plus wheezing. The OR associated with rhinitis were significantly reduced for subjects reporting only recurrent cough or only wheezing (OR=1.43, CI=1.03, 1.99; and OR=1.30, CI=1.07, 1.58, respectively). Recurrent cough and wheezing, when examined independently, showed different patterns of risk factors. Conclusion We found rhinitis to be an independent risk factor for both recurrent cough and wheezing during childhood. Different pathways may be involved in the association of rhinitis with recurrent cough and wheezing.

Background It has long been recognized that many children with asthma outgrow the disease after the onset of puberty, but little is known about genetic factors influencing this outcome Objectives The aim of the present study was to determine whether the polymorphisms at codons 16 and 27 of the β 2 -adrenoceptor are significant predictors of the persistence of asthma during adolescence Design and participants We used data from the prospective Tucson Children’s Respiratory Study. Children were genotyped for the polymorphisms at codons 16 and 27. The presence of wheezing/asthma was assessed by questionnaire from age 6 years up to the reported onset of puberty (prepubertal period) and after the onset of puberty up to age 16 years (adolescence) Results Among children who wheezed in the prepubertal period (n = 168), subjects homozygous for Gly at codon 16 were at significantly increased risk for persistent wheezing after puberty, as compared with carriers of the other genotypes (relative risk [RR], 1.43; 95% confidence interval [CI], 1.06 to 1.92; p = 0.019). This relation was present among boys (RR, 2.17; 95% CI, 1.41 to 3.36) but not girls (RR, 0.85; 95% CI, 0.55 to 1.30), and increased linearly according to the frequency of wheezing episodes after the onset of puberty. These findings persisted after adjusting for ethnicity and other potential confounders and after selecting only white children. The polymorphism at codon 27 showed no relation with risk for persistent wheezing Conclusions This study provides evidence for a strong gender-specific effect of the Gly16 polymorphism on the persistence of asthma after the onset of puberty

Background: In cross-sectional clinical studies, rhinitis has been shown to be strongly associated with co-existing chronic cough. However, to date, this association has been poorly delineated from a prospective and epidemiological standpoint. Methods: We used data from the ‘Pisa Prospective Study’, a population-based longitudinal cohort study composed of a baseline and a follow-up survey taken approximately 5 years apart from each other. Information on cough, rhinitis, and other risk factors was collected by standardized questionnaire. Cough apart from colds was defined as either ‘chronic’ (most days for at least 3 months for at least two consecutive years) or ‘occasional’ (if the three above temporal conditions were not met). ‘Any’ cough was defined as the presence of either occasional or chronic cough. Results: Complete information was available for 1670 subjects who were ≥15 years old and had no positive history of cough apart from colds at the baseline survey. Among them, 299 (18%) had rhinitis at baseline. By the follow-up survey, 16% of the subjects with rhinitis had developed any cough apart from colds, as compared with only 10% of the subjects without rhinitis (OR 1.7, 95% CI 1.2–2.5, P

Objectives The purpose of this study was to quantify the echocardiographic abnormalities in probands who were newly diagnosed with arrhythmogenic right ventricular dysplasia (ARVD). Background The diagnosis of ARVD remains challenging. The Multidisciplinary Study of Right Ventricular Dysplasia was initiated to characterize the cardiac structural, clinical, and genetic aspects of ARVD. Methods Detailed echocardiograms were performed in 29 probands and compared with echoes from 29 normal control patients matched for age, gender, body size, and year of echo. Right atrial (RA) and right ventricular (RV) chamber dimensions, RV regional function, and the presence of morphologic abnormalities (hyper-reflective moderator band, trabecular derangement, and sacculations) were assessed. The RV systolic function was calculated as RV fractional area change (FAC). Results The RV dimensions were significantly increased, and RV FAC was significantly decreased in probands versus control patients (27.2 ± 16 mm vs. 41.0 ± 7.1 mm, p = 0.0003). The right ventricular outflow tract (RVOT) was the most commonly enlarged dimension in ARVD probands (37.9 ± 6.6 mm) versus control patients (26.2 ± 4.9 mm, p 30 mm occurred in 89% of probands and 14% of controls. The RV morphologic abnormalities were present in many probands (trabecular derangement in 54%, hyper-reflective moderator band in 34% and sacculations in 17%) but not in controls. Conclusions Probands with ARVD have significant RA and RV enlargement and decreased RV function, which can be easily assessed on standard echocardiographic imaging. These parameters should be measured when ARVD is suspected and compared with normal values.

Background: For several years, asthma and COPD have been regarded as distinct entities, with distinct clinical courses. However, despite distinctive physiologic features at the time of diagnosis, and different risk factors, the two diseases over time may develop features that are quite similar. Study objective: To evaluate the association between physician-diagnosed asthma and the subsequent development of COPD in a cohort of 3,099 adult subjects from Tucson, AZ. Design and methods: A prospective observational study. Participants completed up to 12 standard respiratory questionnaires and 11 spirometry lung function measurements over a period of 20 years. Survival curves (with time to development of COPD as the dependent variable) were compared between subjects with asthma and subjects without asthma at the initial survey. Results: Subjects with active asthma (n = 192) had significantly higher hazard ratios than inactive (n = 156) or nonasthmatic subjects (n = 2751) for acquiring COPD. As compared with nonasthmatics, active asthmatics had a 10-times-higher risk for acquiring symptoms of chronic bronchitis (95% confidence interval [CI], 4.94 to 20.25), 17-times-higher risk of receiving a diagnosis of emphysema (95% CI, 8.31 to 34.83), and 12.5-times-higher risk of fulfilling COPD criteria (95% CI, 6.84 to 22.84), even after adjusting for smoking history and other potential confounders. Conclusions: Physician-diagnosed asthma is significantly associated with an increased risk for CB, emphysema, and COPD.

Little is known about rates and predictors of remission of childhood asthma after the onset of puberty. We used data collected at ages 6, 8, 11, 13, and 16 years from the Tucson Children's Respiratory Study, a population-based birth cohort. The onset of puberty was defined as the age of appearance of the first pubertal signs as reported by parents. Information on wheezing both before and after onset of puberty (mean +/- SD follow-up from onset of puberty, 4.2 +/- 1 year) was available for 781 children. Of these, 166 had asthma (either frequent wheezing or a physician-confirmed diagnosis plus any wheezing) in at least one survey before puberty. In this group, 58% of the children (97 of 166) reported the presence of wheezing after the onset of puberty (unremitting asthma). In contrast, only 30% (39 of 131) of the children with infrequent wheezing before puberty experienced wheezing episodes after the onset of puberty (unremitting wheezing). In addition to frequent wheezing before puberty, obesity, early onset of puberty, active sinusitis, and skin test sensitization were significant and independent predictors of unremitting asthma after the onset of puberty. Our findings from a population-based longitudinal cohort challenge the commonly held view that asthma usually remits during adolescence.

The objective of this study was to determine the limits for repeatability of FEV1, FVC, and PEF during spirometry test sessions in adult outpatients. A retrospective chart review of 18,000 consecutive patients, aged 20 to 90 years, referred to a large outpatient pulmonary function laboratory for testing was performed. Measurements included the differences between the highest and second-highest FVC (dFVC), FEV1 (dFEV1), and PEF (dPEF), from prebronchodilator spirometry, and anthropometric factors. Ninety percent of the patients were able to reproduce FEV1 within 120 ml (6.1%), FVC within 150 ml (5.3%), and PEF within 0.80 L (12%). Patient characteristics, such as sex, age, height, smoking status, and FEV1 (% predicted), had very little effect on repeatability, explaining only 2 to 4% of the variation in repeatability (expressed in milliliters). We conclude that the ability of patients to meet or exceed spirometry repeatability goals does not depend on patient characteristics when testing is performed by experienced personnel. The current American Thoracic Society repeatability goal of 200 ml for FEV1 and FVC may be too lenient.

Study objectives The Tucson Children's Assessment of Sleep Apnea (TuCASA) study is designed to investigate the prevalence and correlates of objectively measured sleep-disordered breathing (SDB) in preadolescent children. This article describes the parental report of sleep symptoms associated with SDB in Hispanic and white children. Design A 13-question sleep habits screening questionnaire designed to assess the severity of sleep-related symptoms associated with SDB in children 4 to 11 years of age. Setting Questionnaires were completed by the parents of children attending elementary school in the Tucson Unified School District, Tucson, AZ. Participants There were 1,494 questionnaires returned, which comprised a sample of whites (38%), Hispanics (45%), and other races (17%). Of these questionnaires, 1,214 were returned for the children of white (45.8%; 556 children) or Hispanic (54.2%; 658 children) ethnicity only. The primary analysis was completed on these 613 boys (50.5%) and 601 girls (49.5%). Results In the total sample of 1,494 children, parents were more likely to report excessive daytime sleepiness (EDS) in female children than in male children (p Conclusions Hispanic children in the population-based TuCASA study experienced more frequent symptoms associated with SDB, such as SN, EDS, WITAP, and LPs, than did white children. Children with LPs are 2.4 times more likely to have SN, 2.5 times more likely to have EDS, and were 2.1 times more likely to be between the ages of 8 and 11 years. Children with EDS were 3.2 times more likely to have SN, 5.7 times more likely to have WITAP, and were 1.6 times more likely to be a girl.

Background: Although it is defined as cough and sputum production for at least 3 months per year for at least 2 consecutive years, difficulties exist in the use of the term chronic bronchitis for clinical diagnosis. In particular, the relationship between diagnosis and symptoms has been difficult to ascertain. Study objectives: To determine, in a large epidemiologic study, the degree to which a new self-reported diagnosis of chronic bronchitis (NCBR) satisfies the symptom criteria for that diagnosis, and to determine the relationship between self-reported physician-confirmed diagnoses and symptom criteria. Methods: We analyzed data obtained from the Tucson Epidemiologic Study of Obstructive Lung Diseases. Using responses to standardized respiratory questionnaires administered to 4,034 subjects, those with NCBRs were selected and assessed as to whether they met symptom criteria for that diagnosis. Descriptive statistics pertaining to gender, age, and smoking status were obtained. Furthermore, we determined how often symptom criteria were met among a subset of subjects with physician-confirmed self-reported diagnoses. Results: Of 481 subjects with NCBRs, only 56 subjects (11.6%) met the required symptom criteria. Men compared with women and current smokers compared with ex-smokers or neversmokers were more likely to meet symptom criteria. Four hundred fifteen of 481 subjects with NCBRs had physician-confirmed self-reported diagnoses. Of these, only 52 subjects (12.5%) met symptom criteria. Within the subgroup of subjects who met symptom criteria, higher percentages were observed in the older age groups, but this was not statistically significant. Conclusion: Only a minority of subjects with NCBRs satisfy the symptom criteria of cough and sputum production for at least 3 months per year for at least 2 consecutive years. This relationship holds true even among those with physician-confirmed self-reported diagnoses. (CHEST 2002; 122:1234 –1239)

Out-of-hospital hypotension has been associated with increased mortality in traumatic brain injury. The association of traumatic brain injury mortality with the depth or duration of out-of-hospital hypotension is unknown. We evaluated the relationship between the depth and duration of out-of-hospital hypotension and mortality in major traumatic brain injury.We evaluated adults and older children with moderate or severe traumatic brain injury in the preimplementation cohort of Arizona's statewide Excellence in Prehospital Injury Care study. We used logistic regression to determine the association between the depth-duration dose of hypotension (depth of systolic blood pressure90 mm Hg integrated over duration [minutes] of hypotension) and odds of inhospital death, controlling for significant confounders.There were 7,521 traumatic brain injury cases included (70.6% male patients; median age 40 years [interquartile range 24 to 58]). Mortality was 7.8% (95% confidence interval [CI] 7.2% to 8.5%) among the 6,982 patients without hypotension (systolic blood pressure ≥90 mm Hg) and 33.4% (95% CI 29.4% to 37.6%) among the 539 hypotensive patients (systolic blood pressure90 mm Hg). Mortality was higher with increased hypotension dose: 0.01 to 14.99 mm Hg-minutes 16.3%; 15 to 49.99 mm Hg-minutes 28.1%; 50 to 141.99 mm Hg-minutes 38.8%; and greater than or equal to 142 mm Hg-minutes 50.4%. LogIn this study, the depth and duration of out-of-hospital hypotension were associated with increased traumatic brain injury mortality. Assessments linking out-of-hospital blood pressure with traumatic brain injury outcomes should consider both depth and duration of hypotension.