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1.  Childhood pneumonia increases risk for chronic obstructive pulmonary disease: the COPDGene study 
Respiratory Research  2015;16(1):115.
Development of adult respiratory disease is influenced by events in childhood. The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined. We hypothesize that childhood pneumonia is a risk factor for reduced lung function and COPD in adult smokers.
COPD cases and control smokers between 45–80 years old from the United States COPDGene Study were included. Childhood pneumonia was defined by self-report of pneumonia at <16 years. Subjects with lung disease other than COPD or asthma were excluded. Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans.
Of 10,192 adult smokers, 854 (8.4 %) reported pneumonia in childhood. Childhood pneumonia was associated with COPD (OR 1.40; 95 % CI 1.17-1.66), chronic bronchitis, increased COPD exacerbations, and lower lung function: post-bronchodilator FEV1 (69.1 vs. 77.1 % predicted), FVC (82.7 vs. 87.4 % predicted), FEV1/FVC ratio (0.63 vs. 0.67; p < 0.001 for all comparisons). Childhood pneumonia was associated with increased airway wall thickness on CT, without significant difference in emphysema. Having both pneumonia and asthma in childhood further increased the risk of developing COPD (OR 1.85; 95 % CI 1.10-3.18).
Children with pneumonia are at increased risk for future smoking-related lung disease including COPD and decreased lung function. This association is supported by airway changes on chest CT scans. Childhood pneumonia may be an important factor in the early origins of COPD, and the combination of pneumonia and asthma in childhood may pose the greatest risk.
Clinical trials registration, NCT00608764 (Active since January 28, 2008).
Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0273-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4578796  PMID: 26392057
2.  Wheezing symptoms and parental asthma are associated with a doctor diagnosis of asthma in children with sickle cell anemia 
The Journal of pediatrics  2013;164(4):821-826.e1.
To identify factors associated with asthma associated with increased sickle cell anemia (SCA).
Study design
Children with SCA (n=187; mean age 9.6 years, 48% male) were classified as having “asthma” based on parent report of doctor diagnosis plus prescription of asthma medication (n=53) or “no asthma” based on the absence of these features (n=134). Pain and acute chest syndrome (ACS) events were collected prospectively.
Multiple variable logistic regression model identified three factors associated with asthma: parent with asthma (p=0.006), wheezing causing shortness of breath (p=0.001), and wheezing after exercise (p < 0.001). When two or more features were present, model sensitivity was 100%. When none of the features were present, model sensitivity was 0%. When only one feature was present, model sensitivity was also 0% and presence of 2 or more positive allergy skin tests, airway obstruction on spirometry, and bronchodilator responsiveness did not improve clinical utility. ACS incident rates were significantly higher in individuals with asthma than those without asthma (IRR 2.21, CI 1.31-3.76); pain rates were not (IRR 1.28, CI 0.78-2.10).
For children with SCA, having a parent with asthma and specific wheezing symptoms are the best features to distinguish those with and without parent report of a doctor diagnosis of asthma and identify those at higher risk for ACS events. The value of treatment for asthma in prevention of SCA morbidity needs to be studied.
PMCID: PMC3962704  PMID: 24388323
Parental history of asthma; Wheezing symptoms; Allergy to aeroallergens
3.  Detection of Intestinal Protozoa in the Clinical Laboratory 
Journal of Clinical Microbiology  2014;52(3):712-720.
Despite recent advances in diagnostic technology, microscopic examination of stool specimens remains central to the diagnosis of most pathogenic intestinal protozoa. Microscopy is, however, labor-intensive and requires a skilled technologist. New, highly sensitive diagnostic methods have been developed for protozoa endemic to developed countries, including Giardia lamblia (syn. G. intestinalis/G. duodenalis) and Cryptosporidium spp., using technologies that, if expanded, could effectively complement or even replace microscopic approaches. To date, the scope of such novel technologies is limited and may not include common protozoa such as Dientamoeba fragilis, Entamoeba histolytica, or Cyclospora cayetanensis. This minireview describes canonical approaches for the detection of pathogenic intestinal protozoa, while highlighting recent developments and FDA-approved tools for clinical diagnosis of common intestinal protozoa.
PMCID: PMC3957779  PMID: 24197877
4.  Recurrent, severe wheezing is associated with morbidity and mortality in adults with sickle cell disease 
American journal of hematology  2011;86(9):756-761.
Prior studies of asthma in children with sickle cell disease (SCD) were based on reports of a doctor-diagnosis of asthma with limited description of asthma features. Doctor-diagnoses of asthma may represent asthma or wheezing unrelated to asthma. Objectives of this study were to determine if asthma characteristics are present in adults with a doctor-diagnosis of asthma and/or wheezing, and to examine the relationship between doctor-diagnosis of asthma, wheezing and SCD morbidity. This was an observational cohort study of 114 adults with SCD who completed respiratory symptom questionnaires and had serum IgE measurements. A subset of 79 participants completed pulmonary function testing. Survival analysis was based on a mean prospective follow-up of 28 months and data were censored at the time of death or loss to follow-up. Adults reporting a doctor-diagnosis of asthma (N = 34) were more likely to have features of asthma including wheeze, eczema, family history of asthma, and an elevated IgE level (all P < 0.05). However, there was no difference in pain or ACS rate, lung function, or risk of death between adults with and without a doctor-diagnosis of asthma. In contrast, adults who reported recurrent, severe episodes of wheezing (N = 34), regardless of asthma, had twice the rates of pain and ACS, decreased lung function and increased risk of death compared with adults without recurrent, severe wheezing. Asthma features were not associated with recurrent, severe wheezing. Our data suggest that wheezing in SCD may occur independently of asthma and is a marker of disease severity.
PMCID: PMC4103016  PMID: 21809369
6.  Risk Factors for Increased ED Utilization in a Multinational Cohort of Children with Sickle Cell Disease 
Academic Emergency Medicine  2012;19(6):664-672.
To identify clinical, social, and environmental risk factors for increased emergency department (ED) use in children with sickle cell disease (SCD).
This study was a secondary analysis of ED utilization data from the international multicenter Silent Cerebral Infarct Transfusion (SIT) trial. Between December 2004 and June 2010, baseline demographic, clinical, and laboratory data were collected from children with SCD participating in the trial. The primary outcome was the frequency of ED visits for pain. A secondary outcome was the frequency of ED visits for acute chest syndrome.
The sample included 985 children from the US, Canada, England, and France, for a total of 2,955 patient-years of data. There were 0.74 ED visits for pain per patient-year. A past medical history of asthma was associated with an increased risk of ED utilization for both pain (RR = 1.28, 95% CI = 1.04 to 1.58) and acute chest syndrome (RR = 1.60, 95% CI = 1.03 to 2.49). Exposure to environmental tobacco smoke in the home was associated with 73% more ED visits for acute chest syndrome (RR 1.73, 95% CI = 1.09 to 2.74). Each $10,000 increase in household income was associated with 5% fewer ED visits for pain (RR 0.95, 95% CI = 0.91 to 1.00, p = 0.05). The association between low income and ED utilization was not significantly different in the USA vs. countries with universal health care (p = 0.51).
Asthma and exposure to environmental tobacco smoke are potentially modifiable risk factors for greater ED use in children with SCD. Low income is associated with greater ED use for SCD pain in countries with and without universal health care.
PMCID: PMC3375948  PMID: 22687181
7.  In Utero Smoke Exposure and Impaired Response to Inhaled Corticosteroids in Children with Asthma 
Few studies have examined the effects of in utero smoke exposure (IUS) on lung function in children with asthma, and there are no published data on the impact of IUS on treatment outcomes in asthmatic children.
To explore whether IUS exposure is associated with increased airway responsiveness among children with asthma, and whether IUS modifies the response to treatment with inhaled corticosteroids (ICS).
To assess the impact of parent-reported IUS exposure on airway responsiveness in childhood asthma we performed a repeated-measures analysis of methacholine PC20 data from the Childhood Asthma Management Program (CAMP), a four-year, multicenter, randomized double masked placebo controlled trial of 1041 children ages 5–12 comparing the long term efficacy of ICS with mast cell stabilizing agents or placebo.
Although improvement was seen in both groups, asthmatic children with IUS exposure had on average 26% less of an improvement in airway responsiveness over time compared to unexposed children (p=.01). Moreover, while children who were not exposed to IUS who received budesonide experienced substantial improvement in PC20 compared to untreated children (1.25 fold-increase, 95% CI 1.03, 1.50, p=.02) the beneficial effects of budesonide were attenuated among children with a history of IUS exposure (1.04 fold-increase, 95% CI 0.65, 1.68, p=.88).
IUS reduces age-related improvements in airway responsiveness among asthmatic children. Moreover, IUS appears to blunt the beneficial effects of ICS use on airways responsiveness. These results emphasize the importance of preventing this exposure through smoking cessation counseling efforts with pregnant women.
PMCID: PMC2937829  PMID: 20673983
asthma; in utero smoke exposure; airway responsiveness; inhaled corticosteroids
8.  Violence, Abuse, and Asthma in Puerto Rican Children 
Rationale: Puerto Ricans have the highest prevalence of and morbidity from asthma of all ethnic groups in the United States. One potential contributor to the high burden of asthma in Puerto Rican children is exposure to stress and violence.
Objectives: To examine whether exposure to stress and violence is associated with an increased risk of asthma among Puerto Rican children.
Methods: This study was a population-based probability sample of children in the San Juan and Caguas metropolitan areas in Puerto Rico. Information was collected in a household survey of 1,213 children and their primary caretakers.
Measurements and Main Results: The prevalence of lifetime physician-diagnosed asthma was 39.6%. In the year before the survey, 14% of children had witnessed an act of violence, 7% had been victims of violence, and 6% had been victims of physical or sexual abuse. Although stressful life events and exposure to neighborhood violence were not associated with asthma, a history of physical or sexual abuse was associated with approximately twice the odds of current asthma (odd ratio [OR], 2.52; 95% confidence interval [CI], 1.27–5.00), health care use for asthma (OR, 1.95; 95% CI, 0.96–3.96), and medication use for asthma (OR, 2.35; 95% CI, 1.05–5.26).
Conclusions: Physical or sexual abuse is associated with high asthma morbidity among Puerto Rican children. To our knowledge, this is the first report of an association between childhood abuse and asthma. Our findings highlight the importance of screening for asthma among victims of childhood abuse, and to be aware of the possibility of physical or sexual abuse among children with asthma.
PMCID: PMC2542427  PMID: 18556622
asthma; children; stress; violence; abuse

Results 1-8 (8)