Eosinophilic plastic bronchitis: Case series and review of the literature.

Plastic bronchitis is a term used to describe group of life-threatening disorders characterized by the presence of large obstructing casts in the airways. Eosinophilic plastic bronchitis is a subtype of plastic bronchitis that occurs mainly in children and has not been well-described in the literature. Patients may have a history of asthma or atopy, but many do not. They often present with cough and wheezing, and frequently have complete collapse of one lung seen on imaging. The severity of presentation varies depending on the location of the casts, ranging from mild symptoms to severe airway obstruction and death. Bronchoscopy is often required to both diagnose and treat this condition. A variety of medical therapies have been used, although no formal studies have evaluated their efficacy. Symptoms may resolve after initial cast removal, but in some patients, cast formation recurs. Here, we report a case series of nine patients with eosinophilic plastic bronchitis and review the existing literature of this condition.

Pulmonary function tests in extremely low gestational age infants at one year of age.

RATIONALE: Identifying neonatal and post-discharge exposures among extremely low gestational age newborns (ELGANs) that drive increased pulmonary morbidity and abnormal lung function at 1 year of age proves challenging. OBJECTIVE: The NIH-sponsored Prematurity and Respiratory Outcomes Program (PROP), evaluated infant pulmonary function tests (iPFTs) at 1 year corrected age to determine which demographic and clinical factors are associated with abnormal lung function. METHODS: iPFTs were performed on a PROP subcohort of 135 participants following Institutional Review Board (IRB)-approved written consent. Demographic data, Neonatal Intensive Care Unit (NICU) clinical care, and post-NICU exposures were analyzed for association with iPFTs. MAIN RESULTS: A significant decrease in forced expiratory volume at 0.5 s (FEV0.5 ) and/or forced expiratory flows at 75% of forced vital capacity (FEF75 ), were associated with male sex and African American race. Clinical factors including longer duration of ventilatory support, exposure to systemic steroids, and weight less than the 10th percentile at 36 weeks postmenstrual age were also associated with airflow obstruction, whereas supplemental oxygen requirement and bronchopulmonary dysplasia were not. Additionally, the need for respiratory medications, technology, or hospitalizations during the first year, ascertained by a quarterly survey, were the only post-NICU factors associated with decreased FEV0.5 and FEF75 . Only 7% of infants had reversible airflow obstruction. CONCLUSIONS: Neonatal demographic factors, respiratory support in the NICU, and a history of greater post-NICU medical utilization for respiratory disease had the strongest association with lower lung function at 1 year in ELGANs.

Medical and Social Determinants of Health Associated with Intensive Care Admission for Asthma in Children.

RATIONALE: Risk factors for severe asthma exacerbations in children requiring admission to the intensive care unit (ICU) may occur in variety of medical, environmental, economic, and socioeconomic domains. OBJECTIVES: We sought to characterize medical and sociodemographic risk factors among children who required admission to the intensive care unit for asthma. METHODS: Data were obtained from the Greater Cincinnati Asthma Risk Study, a population-based, prospective, observational cohort of children admitted for treatment of acute asthma or bronchodilator-responsive wheezing. Data collected on 774 children included race, socioeconomic status, allergen sensitization, environmental exposures, psychosocial strain, and financial hardship. Analyses compared children admitted to the ICU to those admitted to a medical inpatient unit. MEASUREMENTS AND MAIN RESULTS: One hundred sixty-one (20.9%) children required admission to intensive care. There was no difference in sex, race, insurance status, caregiver educational level, income, financial strain, psychological distress, or marital status between the ICU and non-ICU cohorts. Risk for medication nonadherence assessed by parent report was not different between groups. Although previous hospital admission or emergency department visit history did not differ between the groups, prior ICU admission was more common among those admitted to the ICU at the index admission (27 vs. 16%, P = 0.002). Children requiring intensive care admission were more likely to be sensitized to multiple aeroallergens. Exposure to cigarette smoke (measured as salivary cotinine), although a risk factor for hospital admission, was negatively associated with risk of ICU admission. CONCLUSIONS: Social and economic risk factors typically predictive of increased asthma morbidity, including exposure to tobacco smoke, were not associated with ICU admission among a population of children admitted to the hospital for treatment of acute asthma. Intrinsic disease factors, including allergic sensitization, may be more important predictors of ICU admission.

Pulmonary Morbidity in Infancy after Exposure to Chorioamnionitis in Late Preterm Infants.

RATIONALE: Chorioamnionitis is an important cause of preterm birth, but its impact on postnatal outcomes is understudied. OBJECTIVES: To evaluate whether fetal exposure to inflammation is associated with adverse pulmonary outcomes at 6 to 12 months' chronological age in infants born moderate to late preterm. METHODS: Infants born between 32 and 36 weeks' gestational age were prospectively recruited (N = 184). Chorioamnionitis was diagnosed by placenta and umbilical cord histology. Select cytokines were measured in samples of cord blood. Validated pulmonary questionnaires were administered (n = 184), and infant pulmonary function testing was performed (n = 69) between 6 and 12 months' chronological age by the raised volume rapid thoracoabdominal compression technique. MEASUREMENTS AND MAIN RESULTS: A total of 25% of participants had chorioamnionitis. Although infant pulmonary function testing variables were lower in infants born preterm compared with historical normative data for term infants, there were no differences between infants with chorioamnionitis (n = 20) and those without (n = 49). Boys and black infants had lower infant pulmonary function testing measurements than girls and white infants, respectively. Chorioamnionitis exposure was associated independently with wheeze (odds ratio [OR], 2.08) and respiratory-related physician visits (OR, 3.18) in the first year of life. Infants exposed to severe chorioamnionitis had increased levels of cord blood IL-6 and greater pulmonary morbidity at age 6 to 12 months than those exposed to mild chorioamnionitis. Elevated IL-6 was associated with significantly more respiratory problems (OR, 3.23). CONCLUSIONS: In infants born moderate or late preterm, elevated cord blood IL-6 and exposure to histologically identified chorioamnionitis was associated with respiratory morbidity during infancy without significant changes in infant pulmonary function testing measurements. Black compared with white and boy compared with girl infants had lower infant pulmonary function testing measurements and worse pulmonary outcomes.

Pregnancy without progesterone in horses defines a second endogenous biopotent progesterone receptor agonist, 5α-dihydroprogesterone.

One of the most widely accepted axioms of mammalian reproductive biology is that pregnancy requires the (sole) support of progesterone, acting in large measure through nuclear progesterone receptors (PRs) in uterine and cervical tissues, without which pregnancy cannot be established or maintained. However, mares lack detectable progesterone in the latter half of pregnancy. Instead of progesterone, several (mainly 5α-reduced) pregnanes are elevated and have long been speculated to provide progestational support in lieu of progesterone itself. To the authors' knowledge, evidence for the bioactivity of a second potent endogenously synthesized pregnane able to support pregnancy in the absence of progesterone has never before been reported. The 5α-reduced progesterone metabolite dihydroprogesterone (DHP) was shown in vivo to stimulate endometrial growth and progesterone-dependent gene expression in the horse at subphysiological concentrations and to maintain equine pregnancy in the absence of luteal progesterone in the third and fourth weeks postbreeding. Results of in vitro studies indicate that DHP is an equally potent and efficacious endogenous progestin in the horse but that the PR evolved with increased agonistic potency for DHP at the expense of potency toward progesterone based on comparisons with human PR responses. Sequence analysis and available literature indicate that the enzyme responsible for DHP synthesis, 5α-reductase type 1, also adapted primarily to metabolize progesterone and thereby to serve diverse roles in the physiology of pregnancy in mammals. Our confirmation that endogenously synthesized DHP is a biopotent progestin in the horse ends decades of speculation, explaining how equine pregnancies survive without measurable circulating progesterone in the last 4 to 5 mo of gestation.

Eastern tent caterpillars (Malacosoma americanum) cause mare reproductive loss syndrome.

A new equine abortigenic disease, mare reproductive loss syndrome (MRLS), was recognized and significantly impacted the Ohio Valley in the springs of 2001 and 2002. MRLS caused approximately 330 million US dollars in losses in 2001. An epidemiological investigation of MRLS associated occurrence of the disease with exposure to eastern tent caterpillars (M. americanum). This work investigates the epidemiological association between M. americanum and MRLS to determine if this association was correlative or causative. A pilot study and simulated exposure to M. americanum and their excreta on pasture grasses. The pilot study advanced exposure of pregnant mares to M. americanum materials and 18 of the 29 mares in the study aborted with symptoms of MRLS before other cases were reported in the region. In, three of seven mares exposed to M. americanum aborted, while mares in control (n=6) and M. americanum frass (n=7) treatments had no losses. In, mares were fed frozen insect larvae in feed buckets mixed with oats. Abortions occurred in three of five mares receiving frozen M. americanum, while mares that were fed autoclaved M. americanum (n=5) or frozen gypsy moth larvae (n=4) had no abortions due to MRLS. In, M. americanum larvae were dissected and fractionated. Statistically significant numbers of abortions occurred only in the positive control group and in association with the M. americanum exoskeleton. All abortions induced by exposure to M. americanum exhibited changes in echogenicity of fetal fluids and bacteriological findings post abortion that were consistent with MRLS. These studies support the hypothesis that ingestion of M. americanum larvae induces the MRLS-type equine abortions, and provide experimental evidence that this lepidopteran larva can cause an abortigenic disease in a vertebrate host.