Work Group Report: Perspectives in Diagnosis and Management of Exercise-Induced Bronchoconstriction in Athletes.

Exercise-induced bronchoconstriction, otherwise known as exercise-induced bronchoconstriction with asthma or without asthma, is an acute airway narrowing that occurs as a result of exercise and can occur in patients with asthma. A panel of members from the American Academy of Allergy, Asthma & Immunology Sports, Exercise, & Fitness Committee reviewed the diagnosis and management of exercise-induced bronchoconstriction in athletes of all skill levels including recreational athletes, high school and college athletes, and professional athletes. A special emphasis was placed on the recommendations and regulations set forth by professional athletic organizations after a detailed review of their collective bargaining agreements, substance abuse policies, antidoping program manuals, and the World Anti-Doping Agency antidoping code. The recommendations in this review are based on currently available evidence in addition to providing guidance for athletes of all skill levels as well as their treating physicians to better understand which pharmaceutical and nonpharmaceutical management options are appropriate as well as which medications are permitted or prohibited, and the proper documentation required to remain compliant.

Elevated Testosterone Is Associated with Decreased Likelihood of Current Asthma Regardless of Sex.

BACKGROUND: Asthma prevalence decreases postpuberty in males. Testosterone inhibits airway smooth muscle contraction and attenuates type 2 inflammation. OBJECTIVE: To investigate the relationship between serum testosterone and current asthma prevalence and lung function in a nationally representative data set. METHODS: Serum testosterone and self-reported physician-diagnosed current asthma data were obtained from 7584 participants aged 6 to 80 years from the cross-sectional 2011-2012 National Health and Nutrition Examination Survey. We used logistic regression to test associations between testosterone and current asthma, adjusting for demographic characteristics and stratifying by sex and age; linear regression to evaluate correlations between testosterone and lung function among patients with asthma; and interaction terms to test for effect modification by blood eosinophils and fractional exhaled nitric oxide. RESULTS: Serum testosterone inversely associated with odds of current asthma in both men and women, but this association was nonlinear. Similar protective effect sizes were observed for both sexes after log2-transformation of serum testosterone. For every 1-unit increase in log2 testosterone, the odds of current asthma decreased by 11% in men and 10% in women, although the association was statistically significant in women only among those 12 years or older after multiple imputation. Serum testosterone did not associate with current asthma prevalence among those younger than 12 years. Testosterone associated with increases in FEV1 in participants with asthma of both sexes. Neither blood eosinophils nor fractional exhaled nitric oxide modified the association between testosterone and current asthma. CONCLUSIONS: Serum testosterone inversely associates with current asthma prevalence regardless of sex and correlates with better lung function in a nationally representative database. Androgen therapy for asthma should be further investigated.

Predictors of Financial Capacity in Young Adults.

OBJECTIVE: To examine several predictors of financial capacity as assessed via the Independent Living Scales Money Management (ILS-MM) subtest in a regression correlational design. METHOD: One hundred and five college students were administered measures of financial literacy and financial experience, as well as multiple neuropsychological measures assessing language, processing speed, executive functioning, and arithmetic. Using hierarchical regression analyses, we sought to predict performance on the two subscales of the ILS-MM-Problem Solving and Performance/Information. The former assesses financial knowledge (e.g., defining financial terms such as health insurance) whereas the latter assesses financial abilities (e.g., computing a financial balance). RESULTS: After controlling for demographic variables, financial literacy and experience predicted the Problem Solving subscale, but not the Performance subscale. Neuropsychological measures did not account for additional variance. In contrast, after controlling for demographic variables and financial literacy and financial experience, neuropsychological measures predicted the Performance but not the Problem Solving subscale. The key predictor was the Arithmetic subtest of the Wide Range Achievement Test4, which is not surprising given the mathematical demands of the task. Measures of executive functioning were not related to this measure. CONCLUSIONS: Financial capacity is a broad construct, encompassing many financial abilities and concepts. To predict these, a variety of measures is necessary: financial literacy and experience predict knowledge-based items, whereas neuropsychological measures, especially arithmetic, predict performance-based items. Clinical and research implications of these findings are discussed as well as directions for future investigation.

Hyponatraemia at hospital admission is a predictor of overall mortality.

BACKGROUND: Hyponatraemia is a prognostic marker of increased mortality and morbidity in selected groups of hospitalised patients. The aim of the present study was to examine the prevalence and prognostic significance of hyponatraemia at hospital admission in an unselected population with a broad spectrum of medical and surgical diagnoses. METHODS: Consecutive patients >40 years of age admitted to a general district hospital in Greater Copenhagen between 1 April 1998 and 31 March 1999. Median follow-up time was 5.16 years (range 0-4372 days). Plasma sodium measurements were available in 2960 patients, and hyponatraemia defined as P-Na(+) <137 mmol/L at hospital admission was present in 1105 (37.3 %) patients. RESULTS: One-year mortality was higher for hyponatraemic patients than for normonatraemic patients: 27.5% versus 17.7%. Moreover, hyponatraemia was an independent predictor of short and long-term all-cause mortality after 1 year and after the entire observation period respectively: hazard ratio (HR) 1.6 (95 % confidence interval (CI) 1.4-1.9, P < 0.0001) and HR 1.4 (95 % CI 1.3-1.6, P < 0.0001). Patients with hyponatraemia had longer hospitalisations than patients with normonatraemia: 7.6 (±0.38) days vs 5.6 (±0.21) days, P < 0.001. There was no interaction between hyponatraemia at admission and any admission diagnoses (P > 0.05 for all interaction analyses). CONCLUSION: Hyponatraemia is associated with increased all-cause mortality and longer admission length independently of diagnosis and clinical variables.

The inflammatory biomarker YKL-40 at admission is a strong predictor of overall mortality.

OBJECTIVES: YKL-40 is an inflammatory biomarker associated with disease activity and mortality in patients with diseases characterized by inflammation and tissue remodelling. The aim of this study was to describe the prognostic value of YKL-40 in an unselected patient population. DESIGN: In consecutive patients admitted to hospital during a 1-year period, blood was collected and information regarding final diagnosis and mortality was collected. Median follow-up time was 11.5 years. SETTING: District hospital, Copenhagen, Denmark. PATIENTS: A total of 1407 patients >40 years of age were admitted acutely. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: Median YKL-40 was increased in patients (157 µg L(-1) , range 13-7704 µg L(-1) ) compared to healthy controls (40 µg L(-1) , range 29-58 µg L(-1) ; P < 0.001). Patients with YKL-40 in the highest quartile had a hazard ratio (HR) of 7.1 [95% confidence interval (CI) 4.2-12.0] for all-cause mortality in the first year and 3.4 (95% CI 2.8-4.2) in the total study period, compared to those in the lowest quartile (HR = 1). The HR for death for all patients with YKL-40 above the normal age-corrected 95th percentile was 2.1 (95% CI 1.6-2.7) after 1 year and 1.5 (95% CI 1.3-1.7) during the total study period, compared to patients with YKL-40 below the age-corrected 95th percentile. The results of multivariable analysis showed that YKL-40 was an independent biomarker of mortality; this was most significant in the first year. YKL-40 was a marker of prognosis in all disease categories. The HR for death was increased in patients with YKL-40 above the normal age-corrected 95th percentile in healthy subjects independent of type of disease (all P < 0.001). CONCLUSION: The level of YKL-40 at admission is a strong predictor of overall mortality, independent of diagnosis and could be useful as a biomarker in the acute evaluation of all patients.

N-terminal proBNP and mortality in hospitalised patients with heart failure and preserved vs. reduced systolic function: data from the prospective Copenhagen Hospital Heart Failure Study (CHHF).

UNLABELLED: Preserved systolic function among heart failure patients is a common finding, a fact that has only recently been fully appreciated. The aim of the present study was to examine the value of NT-proBNP to predict mortality in relation to established risk factors among consecutively hospitalised heart failure patients and secondly to characterise patients in relation to preserved and reduced systolic function. MATERIAL: At the time of admission 2230 consecutively hospitalised patients had their cardiac status evaluated through determinations of NT-proBNP, echocardiography, clinical examination and medical history. Follow-up was performed 1 year later in all patients. RESULTS: 161 patients fulfilled strict diagnostic criteria for heart failure (HF). In this subgroup of patients 1-year mortality was approximately 30% and significantly higher as compared to the remaining non-heart failure population (approx. 16%). Using univariate analysis left ventricular ejection fraction (LVEF), New York Heart Association classification (NYHA) and plasma levels of NT-proBNP all predicted mortality independently. However, regardless of systolic function, age and NYHA class, risk-stratification was provided by measurements of NT-proBNP. Having measured plasma levels of NT-proBNP, LVEF did not provide any additional prognostic information on mortality among heart failure patients (multivariate analysis). CONCLUSION: The results show that independent of LVEF, measurements of NT-proBNP add additional prognostic information. It is concluded that NT-proBNP is a strong predictor of 1-year mortality in consecutively hospitalised patients with heart failure with preserved as well as reduced systolic function.

NT-proBNP: a new diagnostic screening tool to differentiate between patients with normal and reduced left ventricular systolic function.

OBJECTIVE: To evaluate whether measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) can be used to differentiate patients with normal and reduced left ventricular ejection fraction (LVEF) in an unselected consecutive group of hospital inpatients. SETTING: City general hospital, Copenhagen, Denmark. PATIENTS AND DESIGN: During a 10 month period 2230 admissions to a city general hospital (80% of targeted patients) had an echocardiographic evaluation of left ventricular function, a comprehensive clinical evaluation, and blood analysis of N-terminal-pro-brain natriuretic peptide (NT-proBNP) within 24 hours of admission. Exclusions resulted from lack of informed consent or failure to obtain the required evaluations before death or discharge from hospital. Echocardiography was unsatisfactory in 37 patients, so the final number studied was 2193. RESULTS: A raised NT-proBNP (>or= 357 pmol/l) identified patients with an LVEF of 40% was more than 97%. This probability rapidly decreased to 70% as the measured NT-proBNP increased to 150% of the predicted value. CONCLUSIONS: A single measurement of NT-proBNP at the time of hospital admission provides important information about LVEF in unselected patients.

Munchausen's syndrome presenting as hemoptysis in a 12-year-old girl.

The case of Munchausen's syndrome presenting as hemoptysis in a 12-year-old girl is presented. The features of Munchausen's syndrome are reviewed. Munchausen's syndrome should be included in the differential diagnosis of hemoptysis in a child, especially when accompanied by a dramatic presentation, changing symptoms and negative diagnostic investigations.

Treatment of sleep-disordered breathing in children with myelomeningocele.

The prevalence of moderate to severe sleep-disordered breathing (SDB) in patients with myelomeningocele may be as high as 20%, but little information is available regarding treatment of these patients. To assess the efficacy and complications of treatments for these children, we collected data on 73 patients from seven pediatric sleep laboratories. Obstructive sleep apnea (OSA, n = 30) and central apnea (n = 25) occurred more frequently than central hypoventilation (n = 12). We also describe a sleep-exacerbated restrictive lung disease type of SDB in 6 patients who had hypoxemia during sleep without apnea or central hypoventilation. For each type of SDB, effective treatments were identified in a stepwise process, moving towards more complex and invasive therapies. For OSA, adenotonsillectomy was often ineffective (10/14), whereas nasal continuous positive airway pressure (CPAP) was usually successful (18/21). For central apnea, methylxanthines and/or supplemental oxygen proved sufficient in 2 of 9 and 3 of 6, respectively, but noninvasive positive pressure ventilation was required in 7 children. For central hypoventilation, supplemental oxygen (alone or with methylxanthines), noninvasive positive pressure ventilation, and tracheostomy with positive pressure ventilation were effective in 3, 2, and 2 patients, respectively. Sleep-exacerbated restrictive lung disease always required supplemental oxygen treatment, but in 2 cases also required noninvasive positive pressure ventilation; nutritional and orthopedic procedures also were helpful. Posterior fossa decompression was used for the first three types of SDB, but data were insufficient to delineate specific recommendations for or against its use. In summary, evaluation by an experienced, multidisciplinary team can establish an effective treatment regime for a child with myelomeningocele and SDB.

Leiomyoma of the esophagus associated with bronchial obstruction owing to inflammatory pseudotumor in a child.

Although relatively common in adults, leiomyoma of the esophagus is a rare disorder in children. A single case report describes the coexistence of both esophageal and bronchial leiomyoma in a child. The authors describe the diagnostic and treatment challenges encountered in a 2-year-old boy with coexisting inflammatory pseudotumor and esophageal leiomyoma presenting as massive atelectasis.

Sleep-disordered breathing in Duchenne muscular dystrophy: a preliminary study of the role of portable monitoring.

Although Duchenne muscular dystrophy (DMD) is often associated with sleep disordered breathing (SDB), it is not standard clinical practice to routinely test this population for SDB, and the optimal timing and methodology for such testing has not been established. Our objectives were: 1) to examine the concordance between laboratory polysomnography (PSG) and two portable monitoring systems, and 2) to identify clinical factors associated with the onset of SDB. We performed a cross-sectional pilot study of patients with DMD who were 6 years of age or older, and who were registered at the Alberta Children's and Calgary General Hospitals. Patient symptom and functional rating scores were calculated, and pulmonary function tests, awake oxygen saturation, and capillary blood gases were obtained. PSG was performed according to standard methods, and results were compared with Snoresat(R) (Saga Tech Electronics, Inc.) and EdenTec(R) (Nellcor Puritan Bennett) portable home monitors. Eleven boys were studied. Ten of 11 subjects had normal awake oxygen saturation and capillary blood gases. Median forced vital capacity (FVC) was 70% of predicted values (15-104%). PSG identified 3 boys with severe hypoventilation occurring throughout REM sleep. Reported symptom severity did not predict the patients with significant SDB. All 3 boys with SDB had a severe functional disability and severely reduced FVCs. Portable monitoring in the home identified all patients with abnormal PSG. One additional patient was falsely identified by the EdenTec(R) monitor. We conclude that initial results using Snoresat(R) or EdenTec(R) monitoring equipment for the identification of SDB are promising, but further validation of portable home monitoring is required in this group of patients.

Sleep-disordered breathing in patients with myelomeningocele: the missed diagnosis.

Moderate to severe sleep-disordered breathing (SDB) was identified in 20% (17 of 83) of children with spina bifida/myelomeningocele (SB/MM) at the Montreal Children's Hospital. The prevalence of SDB in patients with SB/MM elsewhere has not been determined. To establish current practices for identifying SDB in patients with SB/MM, questionnaires were sent to the coordinators of the 212 spina-bifida clinics in Canada and in the United States. Eighty-six (41%) questionnaires were returned, representing data on 13 349 patients. Although 67% of the responding centers reported availability of cardiorespiratory sleep studies, only 996 (7.5%) patients with SB/MM had been tested and only 418 (3.1%) patients had been diagnosed with SDB. Across clinics, the prevalence of SDB was directly related to the frequency of testing. Of 380 deaths over the past 10 years, SDB and sudden unexplained death during sleep were identified as the cause of death in 49 (12.8%) and 34 (8.9%) patients, respectively. Moderate to severe SDB may not have been identified in a significant number of patients with SB/MM because they have not been tested.

Diagnostic approach to obstructive sleep apnea in children.

Obstructive sleep apnea syndrome (OSAS) in childhood is a disorder of breathing during sleep characterized by prolonged partial upper airway obstruction and/or intermittent complete obstruction that disrupts normal ventilation during sleep and normal sleep patterns. A spectrum of severity related to the degree of upper airway resistance, to the duration of the disease, to the presence or absence of hypoxemia episodes, and to certain clinical features can be described. Symptomatic children may not fit the criteria for diagnosis established for OSAS in adults; age-specific standards are needed. Both anatomical factors that increase upper airway resistance, e.g. adenotonsillar hypertrophy, and functional processes that decrease upper airway tone, e.g. REM sleep, contribute to the pathogenesis of pediatric OSAS. Sequelae of OSAS in children include neurobehavioural abnormalities, stunting of growth, and cor pulmonale. Both the history and physical examination should target the sleeping child; parents often report loud snoring, difficulty breathing, and obstructive apneas. The gold standard investigation to establish the diagnosis and to quantitate disease severity is overnight polysomnography. Home cardiopulmonary sleep studies have been shown to be an accurate and practical alternative to overnight laboratory polysomnography for routine evaluation of non-complex children with adenotonsillar hypertrophy. Children with documented severe OSAS are at increased post-operative risk for airway compromise and should be observed and monitored carefully. Adenotonsiliectomy is the most common therapy for OSAS in children; as a second-line treatment, the use of nasal CPAP in children with OSAS has been very successful in experienced hands.

An analysis of human sperm chromosome aneuploidy.

A sperm chromosome analysis of 24 men with normal or balanced karyotypes was carried out to study the frequency of sperm chromosome aneuploidy. A total of 3,446 human sperm complements (36-315 per donor) was analyzed after in vitro penetration of hamster eggs. Two sets of donors were studied at two different centers in the United States (center 1) and Spain (center 2). The frequencies of hyperhaploidy and hypohaploidy in control donors were similar between center 1 (1.9% vs. 7.7%) and center 2 (1.8% vs. 10.3%). In carrier donors there were no significant differences between the two centers in the frequency of hyperhaploidy (0.8% vs. 1.9%), but that of hypohaploidy was significantly higher in center 2 (11.0%) than in center 1 (4.6%). A significant excess of hypohaploid complements, as compared to hyperhaploid complements, was found in both centers in both control and carrier donors. The sex ratio was similar in both centers and did not differ significantly from a 1:1 sex ratio. The larger chromosomes in the complement (1, 2, 3, 4, 5, 7, and 10) presented a significantly lower frequency of hypohaploidy, while some of the smaller chromosomes (13, 19, and 21) showed a higher frequency of hypohaploidy than expected. Chromosome 21 and the sex chromosomes showed an increase in the percentage of hyperhaploidy, as compared to other chromosomes, that was close to statistical significance (P = 0.08). Our results reflect a preferential loss of small chromosomes during slide preparation and suggest that chromosome 21 and the sex chromosomes could be more frequently involved in aneuploidy.

An analysis of human sperm chromosome breakpoints.

Sperm chromosome analysis of 19 sperm donors with either normal or balanced karyotypes was carried out in order to explore the nature of sperm chromosome structural aberrations. A total of 2,389 cells (range 36-298/donor) were karyotyped after in vitro penetration of hamster eggs. The median percentage of sperm structural aberrations was 9.3% (SD +/- 4.7; range 0%-17.8%), with a total of 247 breakpoints, of which 220 could be characterized fully. Two sets of donors were studied in two different centers: center 1 (United States) and center 2 (Spain). The frequencies of nonrejoined and rejoined chromosome-type aberrations were very similar between center 1 and center 2: 83.6% and 10.0%, and 75.0% and 10.3%, respectively. Chromatid-type aberrations were more frequent in center 2 (14.7%) than in center 1 (6.4%) (P = .037). Chromosome 4 had less than the expected number of breakpoints (P < .001). A positive significant correlation was found between sperm breakpoints reported in this study and sites of balanced chromosome de novo rearrangements detected at prenatal diagnosis and reported in the literature (P = .0001).

Segregation analysis of four translocations, t(2;18), t(3;15), t(5;7), and t(10;12), by sperm chromosome studies and a review of the literature.

We examined the meiotic segregation patterns of 444 sperm cells belonging to four reciprocal translocation carriers, t(2;18)(p21;q11.2), t(3;15)(q26.2; q26.1), t(5;7)(q13; p15.1), and t(10;12)(q26.1;p13.3). For the t(2;18) carrier, the frequencies of alternate, adjacent-1, adjacent-2, and 3:1 segregations were 41.9%, 35.2%, 14.4%, and 8.4%, respectively. For the t(3;15) carrier, the segregation pattern was 48% alternate, 36% adjacent-1, 12% adjacent-2, 2% 3:1, and 2% 4:0. One cell was the result of a 4:0 segregation. For the t(5;7) heterozygote, the corresponding segregation frequencies were 40.2%, 26.2%, 16.6%, and 17.0%. This translocation heterozygote showed a higher number of 3:1 segregations than adjacent-2 segregations, which is unusual. The t(10;12) segregations were 61.1%, 26.3%, 6.9%, and 5.6%. The percentages of chromosome abnormalities unrelated to the translocation ranged from 0% to 0.6% for aneuploidy and from 5.5% to 10.9% for structural abnormalities. These frequencies are within the ranges for control donors. Sperm chromosome data from the literature on the segregation of 30 reciprocal translocations were reviewed.