Favorable response to asthma-dosed subcutaneous mepolizumab in eosinophilic pneumonia.

Introduction: Mepolizumab targets eosinophils in the treatment of asthma. The dose used for asthma is considerably lower than that used for treating eosinophilic granulomatosis with polyangiitis, a recently approved indication. While intravenous mepolizumab use has reported utility in non-asthma eosinophilic disorders, the efficacy of the subcutaneous asthma dosing of the drug for eosinophilic pneumonia is not known. Case study: A middle-aged female was diagnosed with eosinophilic pneumonia. The patient's clinical/radiologic/laboratory findings, response to treatment, and respiratory function studies are described. Results: A woman, born in 1962, had repeated pneumonia hospitalizations from 2007 through 2010. In October 2010, a lung biopsy showed findings consistent with chronic eosinophilic pneumonia and chronic asthma. The patient also had chronic sinusitis. Long term systemic corticosteroids were prescribed but the patient became oxygen dependent by 2014. Omalizumab was administered for 1 year starting in 2015 without improvement in symptoms. In 2016, mepolizumab 100 mg subcutaneously every 4 weeks was initiated. Symptomatic improvement with decreased oxygen and systemic corticosteroid requirements were noted. A chest CT performed in February 2018 showed marked improvement compared to a study in 2016. Interval spirometric improvements were noted. Peripheral blood eosinophils/mm3 prior to mepolizumab were 237, and while on mepolizumab were 10. Conclusion: Parenchymal eosinophilic lung disease may respond to asthma-dosed mepolizumab. Mepolizumab treatment in asthma where concomitant interstitial disease is suspected, may offer an advantage over omalizumab in the ability to reduce eosinophils not only in airways, but also in lung parenchyma.

Orthotic Management of Deformational Plagiocephaly: Consensus Clinical Standards of Care.

OBJECTIVE: To establish consensus on definitive, actionable standards for the management of deformational plagiocephaly. DESIGN: Three-stage Delphi Survey process based on best practice statements obtained through literature review. SETTING: Electronic survey delivery. PARTICIPANTS: Review panel of 10 multidisciplinary subject matter experts (SMEs); survey panel of 30 cranial orthotists. RESULTS: Fifty-four best practice statements were accepted in four categories: diagnosis, presentation and severity, initiating treatment, and management principles. CONCLUSIONS: Clinical practice can be guided en route to robust evidence as to the efficacy of various plagiocephaly management strategies, in pursuit of definitive standards.

Microfluidic integration for automated targeted proteomic assays.

A dearth of protein isoform-based clinical diagnostics currently hinders advances in personalized medicine. A well-organized protein biomarker validation process that includes facile measurement of protein isoforms would accelerate development of effective protein-based diagnostics. Toward scalable protein isoform analysis, we introduce a microfluidic "single-channel, multistage" immunoblotting strategy. The multistep assay performs all immunoblotting steps: separation, immobilization of resolved proteins, antibody probing of immobilized proteins, and all interim wash steps. Programmable, low-dispersion electrophoretic transport obviates the need for pumps and valves. A three-dimensional bulk photoreactive hydrogel eliminates manual blotting. In addition to simplified operation and interfacing, directed electrophoretic transport through our 3D nanoporous reactive hydrogel yields superior performance over the state-of-the-art in enhanced capture efficiency (on par with membrane electroblotting) and sparing consumption of reagents (ca. 1 ng antibody), as supported by empirical and by scaling analyses. We apply our fully integrated microfluidic assay to protein measurements of endogenous prostate specific antigen isoforms in (i) minimally processed human prostate cancer cell lysate (1.1 pg limit of detection) and (ii) crude sera from metastatic prostate cancer patients. The single-instrument functionality establishes a scalable microfluidic framework for high-throughput targeted proteomics, as is relevant to personalized medicine through robust protein biomarker verification, systematic characterization of new antibody probes for functional proteomics, and, more broadly, to characterization of human biospecimen repositories.

Fatal anaphylaxis in the United States, 1999-2010: temporal patterns and demographic associations.

BACKGROUND: Anaphylaxis-related deaths in the United States have not been well characterized in recent years. OBJECTIVES: We sought to define epidemiologic features and time trends of fatal anaphylaxis in the United States from 1999 to 2010. METHODS: Anaphylaxis-related deaths were identified by using the 10th clinical modification of the International Classification of Diseases system diagnostic codes on death certificates from the US National Mortality Database. Rates were calculated by using census population estimates. RESULTS: There were a total of 2458 anaphylaxis-related deaths in the United States from 1999 to 2010. Medications were the most common cause (58.8%), followed by "unspecified" (19.3%), venom (15.2%), and food (6.7%). There was a significant increase in fatal drug-induced anaphylaxis over 12 years: from 0.27 (95% CI, 0.23-0.30) per million in 1999 to 2001 to 0.51 (95% CI, 0.47-0.56) per million in 2008 to 2010 (P < .001). Fatal anaphylaxis caused by medications, food, and unspecified allergens was significantly associated with African American race and older age (P < .001). Fatal anaphylaxis to venom was significantly associated with white race, older age, and male sex (P < .001). The rates of fatal anaphylaxis to foods in male African American subjects increased from 0.06 (95% CI, 0.01-0.17) per million in 1999 to 2001 to 0.21 (95% CI, 0.11-0.37) per million in 2008 to 2010 (P < .001). The rates of unspecified fatal anaphylaxis decreased over time from 0.30 (95% CI, 0.26-0.34) per million in 1999 to 2001 to 0.09 (95% CI, 0.07-0.11) per million in 2008 to 2010 (P < .001). CONCLUSION: There are strong and disparate associations between race and specific classes of anaphylaxis-related mortality in the United States. The increase in medication-related deaths caused by anaphylaxis likely relates to increased medication and radiocontrast use, enhanced diagnosis, and coding changes.

Domination of heliosheath pressure by shock-accelerated pickup ions from observations of neutral atoms.

The solar wind blows an immense magnetic bubble, the heliosphere, in the local interstellar medium (mostly neutral gas) flowing by the Sun. Recent measurements by Voyager 2 across the termination shock, where the solar wind is slowed to subsonic speeds before entering the heliosheath, found that the shocked solar wind plasma contains only approximately 20 per cent of the energy released by the termination shock, whereas energetic particles above approximately 28 keV contain only approximately 10 per cent; approximately 70 per cent of the energy is unaccounted for, leading to speculation that the unmeasured pickup ions or energetic particles below 28 keV contain the missing energy. Here we report the detection and mapping of heliosheath energetic ( approximately 4-20 keV) neutral atoms produced by charge exchange of suprathermal ions with interstellar neutral atoms. The energetic neutral atoms come from a source approximately 60 degrees wide in longitude straddling the direction of the local interstellar medium. Their energy spectra resemble those of solar wind pickup ions, but with a knee at approximately 11 keV instead of approximately 4 keV, indicating that their parent ions are pickup ions energized by the termination shock. These termination-shock-energized pickup ions contain the missing approximately 70 per cent of the energy dissipated in the termination shock, and they dominate the pressure in the heliosheath.

Age dependent sex disproportion in US asthma hospitalization rates, 2000-2010.

BACKGROUND: Age-stratified sex differences in asthma hospitalizations rates have been reported to be most marked between the ages of 40 and 54 years in New York. It is not known whether age-dependent sex differences in asthma hospitalization rates also exist for the entire United States. OBJECTIVES: To compare sex-specific hospitalization rates for asthma in adults in the United States and to describe the adjusted associations between female sex and age in the fifth to sixth decades of life. METHODS: The National Inpatient Sample databases for 2000-2010 were queried for a principal diagnosis of asthma to calculate the ratio of female to male hospitalization rates for different decades of adult life. Logistic regression modeling was used to determine whether age in the fifth to sixth decades of life had associations with female sex that remained significant after adjusting for comorbidities and demographic features. RESULTS: For all years of the study, there was a distinct peaking in female to male ratio most manifested in the fifth to sixth decades of life. This age grouping was significantly associated with female sex. Models revealed that female sex was significantly associated with this age grouping, even after adjustment for obesity, chronic obstructive pulmonary disease, race, insurance status, discharge year, and smoking. Excluding identifiable repeat admissions also did not abrogate the age grouping association. CONCLUSION: There is a striking propensity of women in their fifth to sixth decades of life to be admitted for asthma, which appears to be independent of many known comorbidities.

Adverse drug effects and angioedema hospitalizations in the United States from 2000 to 2009.

Since angiotensin-converting enzyme (ACE) inhibitors became common treatments, there have been increasing reports of angioedema (AE). AE hospitalization (AEH) trend data in the new millennium are limited. This study calculates hospitalization rates for AEs and describes clinical characteristics of AEHs in the United States, especially as related to specific adverse drug effects (ADEs). The National Inpatient Samples 2000-2009 were queried for AEHs to calculate hospitalization rates and to examine for associations with specified ADEs, certain comorbidities, and demographic features. AEHs requiring intubation or tracheostomy were also examined for associations. There was a significant increase in the AEH rates (3.4 per 10(5) to 5.4 per 10(5)) over the study period (p < 0.0001) and the hospitalization rates for African Americans (AAs) were consistently higher. Throughout the study the proportions of AEH coding any ADEs, or an ADE due to a cardiovascular (CV) or antihypertensive (aHTN) drug increased over time. By 2009, 61.7% AEHs coded an ADE. Of these, 58.7% were caused by CV or aHTN drugs. In AEHs, having an ADE from a CV or aHTN medication had the strongest adjusted associations with hypertension and renal disease as well as with alcohol-related disorders. In AEHs, intubation/tracheostomy had the strongest ADE associations related to CV or aHTN medication (adjusted odds ratio, 1.4; 95% CI, 1.3, 1.6). AEHs continue to increase, but this can only be partially attributed to ACE inhibitor usage. Intubation/tracheostomy appears to be greater in AEHs with ADE due to CV/aHTN drugs. Alcohol-related disorders may have a role in ACE inhibitor-associated AEH.

Perspectives on anaphylaxis epidemiology in the United States with new data and analyses.

Anaphylaxis incidence rates and time trends in the United States have been reported using different data sources and selection methods. Larger studies using diagnostic coding have inherent limitations in sensitivity and specificity. In contrast, smaller studies using chart reviews, including reports from single institutions, have better case characterization but suffer from reduced external validity due to their restricted nature. Increasing anaphylaxis hospitalization rates since the 1990s have been reported abroad. However, we report no significant overall increase in the United States. There have been several reports of increasing anaphylaxis rates in northern populations in the United States, especially in younger people, lending support to the suggestion that higher anaphylaxis rates occur at higher latitudes. We analyzed anaphylaxis hospitalization rates in comparably sized northern (New York) and southern (Florida) states and found significant time trend differences based on age. This suggests that the relationship of latitude to anaphylaxis incidence is complex.

Refractive results with SMILE using lower energy settings in the United States.

PURPOSE: To report the visual and refractive results of small incision lenticule extraction (SMILE) with low energy settings in the United States (US) and to evaluate outcomes for low astigmatism treatment. SETTING: Private clinical practice. DESIGN: Retrospective cohort study. METHODS: This study retrospectively reviewed 462 consecutive eyes that underwent SMILE with lower energy settings. Inclusion criteria included all patients between the ages of 19-39 with myopic astigmatism up to -11.25 diopters (D) spherical equivalent (sphere up to -10.00 D, astigmatism up to -3.00 D), and corrected distance visual acuity of at least 20/25. Eyes with low astigmatism (0.25 D-0.50 D) were also included. Outcome analysis was performed according to the Standard Graphs for Reporting Refractive Surgery at postoperative month (POM) 1, and POM 3-6 when data were available. RESULTS: The mean preoperative spherical equivalent treated was -4.96 ± 2.07; at POM 1, 92% of eyes achieved uncorrected visual acuity (UCVA) of 20/20 or better and maintained visual stability throughout the remainder of the study. At last visit, 431 eyes (93%) achieved UCVA of 20/20 or better, and 461 eyes (99.8%) were 20/25 or better. Ninety-seven (21%) eyes gained at least 1 Snellen line of corrected distance visual acuity and no eyes lost 2 or more lines. Almost all eyes (n = 453, 98%) were within 0.5D of target; 85% of eyes with low astigmatism had ≤0.25 D at last visit compared to 80% of eyes with moderate astigmatism. CONCLUSIONS: SMILE with U.S.-approved low energy settings is safe, predictable, and efficacious and provides patients with a fast visual recovery.

In vitro-in vivo correlations of scalable PLGA-risperidone implants for the treatment of schizophrenia.

PURPOSE: Nonadherence to antipsychotic medications is a major obstacle preventing optimal outcomes for patients with schizophrenia. Extended release systems exist in the form of depot injections, but these formulations exhibit several disadvantages. To address these concerns, we previously demonstrated proof of concept for an antipsychotic implant containing risperidone and the biodegradable polymer poly(lactic-co-glycolic) acid (PLGA). METHODS: We build upon recently published data by utilizing a scalable single-screw extrusion system for the production of PLGA-risperidone implants. Implants were composed of 40% risperidone and 60% PLGA, with varying ratios of lactide to glycolide (50:50, 65:35, 75:25 or 85:15). Risperidone release was assessed in vitro and in vivo in rats, and Level A, B and C correlations (IVIVCs) attempted for all. Bioavailability was verified with locomotor testing RESULTS: Level B analysis yielded the greatest correlation between in vitro and in vivo data (R (2) = 0.9425), while Level C yielded the lowest (R (2) = 0.8336). Although, based on qualitative results, a Level A correlation was not achieved, it did produce an R (2) of 0.9261. Locomotor testing demonstrated that peak serum concentrations coincide with significant reductions in activity. CONCLUSION: Data demonstrate the applicability of our modeling system and advance long-term, implantable antipsychotics toward clinical application.

Clinical associations of delirium in hospitalized adult patients and the role of on admission presentation.

OBJECTIVE: To describe clinical associations of delirium in hospitalized patients and relationships to on admission presentation. DESIGN: Retrospective analysis of an administrative hospitalization database 1998-2007. SETTING: Acute care hospitalizations in the New York State (NYS). MEASUREMENTS: Four categories of diagnosis related group (DRG) hospitalizations were extracted from a NYS administrative database: pneumonia, congestive heart failure, urinary tract/kidney infection (UTI), and lower extremity orthopedic surgery (LEOS) DRGs. These hospitalizations were examined for clinical associations with delirium coding both on and after admission. RESULTS: Delirium was coded in 0.8% of the cohort, of which an on admission diagnosis was present in 59%. On admission delirium was strongly associated with dementia (adjusted odds ratio 0, 95%CI 5.8-6.3) and with adverse drug effects (ADEs) (adjusted odds ratio 4.6, 95%CI 4.3, 5.0). After admission delirium was even more highly associated with ADEs (adjusted odds ratio 22.2, 95%CI 20.7-23.7). The UTI DRG category had the greatest proportion of on admission delirium. However after admission delirium was more common in the LEOS DRG category. Over time, there was a greater increase in delirium proportions in the UTI DRG category, and an overall increase in coding for encephalopathy states (potential alternative delirium descriptors). CONCLUSION: ADEs play an important role in delirium regardless of whether or not it is present on admission. While the finding that most delirium hospitalizations presented on admission suggests that delirium impacts more as a clinical admitting determinant, in-hospital prevention strategies may still have benefit in targeted settings where after admission delirium is more frequent, such as patients with LEOS.

Measured immunoglobulin E in allergic bronchopulmonary aspergillosis treated with omalizumab.

BACKGROUND: The ability to assess adequate reductions in immunoglobulin E (IgE) in allergic bronchopulmonary aspergillosis (ABPA) has been a concern with regards to omalizumab treatment. OBJECTIVE: To describe the clinical course and serial measured IgE levels in two adult patients with elevated IgE levels, hypersensitivity to Aspergillus fumigatus, and bilateral bronchiectasis who were treated with omalizumab. CLINICAL DESCRIPTIONS: Patient 1 met commonly used criteria for ABPA and had a more than 3-fold increase (from 702 to 2462 IU/ml) in measured IgE 4 months after starting omalizumab. Two years after starting omalizumab, the IgE level decreased to baseline (473 IU/ml) even when corticosteroids were discontinued. Patient 2 had near normalization of elevated IgE levels when treated with corticosteroids but IgE levels subsequently rose again to over 10,000 IU/ml. After reducing the IgE level to 586 IU/ml with higher corticosteroid doses, omalizumab was initiated. Twenty months after starting omalizumab, the measured IgE was 510 IU/ml. Based on published omalizumab treatment­associated total/free IgE ratios, the estimated free IgE levels for both patients after more than a year of omalizumab treatment was less than their pre­omalizumab treatment IgE levels. CONCLUSIONS: These data suggest that omalizumab can be beneficial in treating ABPA and that measured IgE levels can still be useful in this context. Noting the pattern of IgE levels associated with ABPA exacerbations and with corticosteroid treatment may help both with achieving an IgE level appropriate for omalizumab treatment and with the interpretation of measured IgE changes associated with omalizumab treatment.

Development and validation of a 4-color multiplexing spinal muscular atrophy (SMA) genotyping assay on a novel integrated digital PCR instrument.

Digital PCR (dPCR) technology has been proven to be highly sensitive and accurate in detecting copy number variations (CNV). However, a higher-order multiplexing dPCR assay for measuring SMN1 and SMN2 copy numbers in spinal muscular atrophy (SMA) samples has not been reported. Described here is a rapid multiplex SMA dPCR genotyping assay run on a fully integrated dPCR instrument with five optical channels. The hydrolysis probe-based multiplex dPCR assay quantifies SMN1, SMN2, and the total SMN (SMN1 + SMN2) while using RPPH1 gene as an internal reference control. The quadruplex assay was evaluated with characterized control DNA samples and validated with 15 blinded clinical samples from a previously published study. SMN1 and SMN2 copy numbers were completely concordant with previous results for both the control and blinded samples. The dPCR-based SMA copy number determination was accomplished in 90 min with a walk-away workflow identical to real-time quantitative PCR (qPCR). In summary, presented here is a simple higher-order multiplexing solution on a novel digital PCR platform to meet the growing demand for SMA genotyping and prognostics.

Safety of bloodless autologous stem cell transplantation in Jehovah's Witness patients.

Due to the curative potential and improvement in progression-free survival (PFS), high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered the standard of care for several hematologic malignancies, such as multiple myeloma, and lymphomas. ASCT typically involves support with blood product transfusion. Thus, difficulties arise when Jehovah's Witness patients refuse blood transfusions. In order to demonstrate the safety of performing "bloodless" ASCT (BL-ASCT), we performed a retrospective analysis of 66 Jehovah's Witnesses patients who underwent BL-ASCT and 1114 non-Jehovah's Witness patients who underwent transfusion-supported ASCT (TF-ASCT) at Cedars-Sinai Medical Center between January 2000 and September 2018. Survival was compared between the two groups. Transplant-related complications, mortality, engraftment time, length of hospital stay, and number of ICU transfers were characterized for the BL-ASCT group. One year survival was found to be 87.9% for both groups (P = 0.92). In the BL-ASCT group, there was one death prior to the 30 days post transplant due to CNS hemorrhage, and one death prior to 100 days due to sepsis. Based on our data, BL-ASCT can be safely performed with appropriate supportive measures, and we encourage community oncologists to promptly refer JW patients for transplant evaluation when ASCT is indicated.

Artificial neural networks-based classification of emotions using wristband heart rate monitor data.

Heart rate variability (HRV) is an objective measure of emotional regulation. This study aimed to estimate the accuracy with which an artificial neural network (ANN) algorithm could classify emotions using HRV data that were obtained using wristband heart rate monitors.Four emotions were evoked during gameplay: pleasure, happiness, fear, and anger. Seven normalized HRV features (i.e., 3 time-domain features, 3 frequency-domain features, and heart rate), which yielded 29,727 segments during gameplay, were collected and analyzed first by statistics and then classified by the trained ANN model.General linear model adjusted for individual differences in HRV showed that all HRV features significantly differed across emotions, despite disparities in their magnitudes and associations. When compared to neutral status (i.e., no emotion evoked), the mean of R-R interval was significantly higher for pleasure and fear but lower for happiness and anger. In addition, pleasure evidenced the HRV features that suggested a superior parasympathetic to sympathetic activation. Happiness was associated with a prominent sympathetic activation. These statistical findings suggest that HRV features significantly differ across emotions evoked by gameplay. When further utilizing ANN-based emotion classification, the accuracy rates for prediction were above 75.0% across the 4 emotions with accuracy rates for classification of paired emotions ranging from 82.0% to 93.4%.For classifying emotion in an individual person, the trained ANN model utilizing HRV features yielded a high accuracy rate in our study. ANN is a time-efficient and accurate means to classify emotions using HRV data obtained from wristband heart rate monitors. Thus, this integrated platform can help monitor and quantify human emotions and physiological biometrics.

Precision cancer monitoring using a novel, fully integrated, microfluidic array partitioning digital PCR platform.

A novel digital PCR (dPCR) platform combining off-the-shelf reagents, a micro-molded plastic microfluidic consumable with a fully integrated single dPCR instrument was developed to address the needs for routine clinical diagnostics. This new platform offers a simplified workflow that enables: rapid time-to-answer; low potential for cross contamination; minimal sample waste; all within a single integrated instrument. Here we showcase the capability of this fully integrated platform to detect and quantify non-small cell lung carcinoma (NSCLC) rare genetic mutants (EGFR T790M) with precision cell-free DNA (cfDNA) standards. Next, we validated the platform with an established chronic myeloid leukemia (CML) fusion gene (BCR-ABL1) assay down to 0.01% mutant allele frequency to highlight the platform's utility for precision cancer monitoring. Thirdly, using a juvenile myelomonocytic leukemia (JMML) patient-specific assay we demonstrate the ability to precisely track an individual cancer patient's response to therapy and show the patient's achievement of complete molecular remission. These three applications highlight the flexibility and utility of this novel fully integrated dPCR platform that has the potential to transform personalized medicine for cancer recurrence monitoring.

Rapid microfabrication of solvent-resistant biocompatible microfluidic devices.

This paper presents a rapid, simple, and low-cost fabrication method to prepare solvent resistant and biocompatible microfluidic devices with three-dimensional geometries. The devices were fabricated in thiolene and replicated from PDMS master with high molding fidelity. Good chemical compatibility for organic solvents allows volatile chemicals in synthesis and analysis applications. The surface can be processed to be hydrophobic or hydrophilic for water-in-oil and oil-in-water emulsions. Monodisperse organic solvent droplet generation is demonstrated to be reproducible in thiolene microchannels without swelling. The thiolene surface prevents cell adhesion but normal cell growth and adhesion on glass substrates is not affected by the adjacent thiolene patterns.

Droplet microfluidics.

Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of "digital fluidic" operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as microreactors ranging from the nano- to femtoliter range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. This review will focus on the various droplet operations, as well as the numerous applications of the system. Due to advantages unique to droplet-based systems, this technology has the potential to provide novel solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics.

Dabska tumor arising in lymphangioma circumscriptum.

We describe a case of Dabska tumor (DT) occurring within a large congenital lymphangioma circumscriptum on the thigh of a 14-year-old female. Diagnostic biopsy showed numerous intravascular papillary projections lined by atypical endothelial cells within the anastomosing vascular channels of a lymphangioma circumscriptum. DT is regarded as a vascular tumor of intermediate malignant potential, most probably of lymphatic origin. Although it has been described in pre-existing lymphangiomas, to the best of our knowledge this is the first case to be described in a pre-existing lymphangioma circumscriptum. During a follow-up of 9 years, the lymphangioma circumscriptum has recurred, but there has been no evidence of DT recurrence or metastasis.

The gender disparity in adult asthma hospitalizations dynamically relates to age.

Although it is known that women have a higher prevalence of asthma than men, it is not known whether and/or how gender differences in asthma severity are affected by age. Asthma hospitalization rates were compared for men and women in New York State from 1990 through 2006 between the ages of 20 and 84. Female and male hospitalization rates were calculated and characterized for the different age intervals. The ratio between female to male hospitalization rates were compared for different age groups. While males showed an overall linear increase in hospitalization rates with increasing age, women had a steeper increase in hospitalization rates followed by a slowing beginning at the ages between 40-54. The ratio of the female to male hospitalization rates was maximal in this age interval, with a mean ratio of 2.41 compared to 1.97 in other ages. For each year, this female to male ratio was consistently higher for the age range between 40 to 54 than for other ages, and this difference remained when admissions associated obesity, tobacco dependence, and chronic non-asthmatic pulmonary disease were excluded. Differences between the hospitalization rates for men and women vary by age. The gender gap in hospitalization rates appears to be maximal between the ages of 40 and 54. This may reflect age related asthma prevalence and/or severity differences between men and women.