Joseph D Spahn

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States

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Publications (95)539.5 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The chitinase-like protein YKL-40 is thought to play a role in inflammation and tissue remodeling. In adults with severe asthma, YKL-40 is expressed in the airway and YKL-40 levels are elevated in the serum.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 06/2014; · 3.45 Impact Factor
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    The Journal of allergy and clinical immunology. 05/2014;
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    ABSTRACT: Novel asthma pharmacotherapy has changed the management of severe childhood asthma. This study determined whether the introduction and use of second-generation inhaled glucocorticoids (GCs), long-acting beta-agonists (LABAs), and combination inhaled GC/LABA (iGC/LABA) products and leukotriene receptor antagonists (LTRAs) have impacted children with severe asthma. A retrospective review of children (aged 6-18 years) referred to National Jewish Health for severe asthma between 2003 and 2007 (current cohort) was performed (n = 65); the results were compared with a published cohort from 1993 to 1997 (historic cohort; n = 164). When comparing the current cohort to the historic cohort, the percentage requiring chronic oral GC therapy (28% versus 51%; p = 0.001), average dose (3.7 ± 2.4 mg/dose versus 16.7 ± 1.4 mg/dose; p < 0.0001), and duration of oral GC use (17.8 ± 8.6 months versus 33.7 ± 3.5 months; p = 0.09) were less. Ninety-seven percent of the current cohort was on a second-generation iGC either alone or in combination with an LABA, 76% were on an LTRA, and 66% were on combination iGC/LABA product, while none of the historic cohort received these medications. In addition, the current cohort had a higher forced expiratory volume in 1 second (84 ± 2.5% versus 76 ± 2% of predicted; p = 0.008), required less albuterol (33 ± 9 inhalations/week versus 71 ± 7 inhalations/week; p = 0.0007), had fewer intubations in the past (13% versus 21%; p = 0.13) and had fewer GC-induced adverse effects compared with the historic cohort. The current cohort required less chronic oral GCs, had better asthma control, and had fewer GC-induced adverse effects compared with the historic cohort studied 10 years ago. This is most likely because of the use of more effective medications for childhood asthma.
    Allergy and Asthma Proceedings 03/2014; 35(2):119-25. · 2.19 Impact Factor
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    ABSTRACT: Background The chitinase-like protein YKL-40 is thought to play a role in inflammation and tissue remodeling. In adults with severe asthma, YKL-40 is expressed in the airway and YKL-40 levels are elevated in the serum. Objective To compare YKL-40 levels in children with severe persistent asthma with those in adults with severe persistent asthma and to determine whether YKL-40 levels correlate with increasing asthma severity in childhood asthma. Methods In this prospective, cross-sectional study, 23 adults and 19 children with severe persistent asthma, 23 children with moderate persistent asthma, and 19 children with mild persistent asthma were enrolled. The following data were collected on each patient: spirometry, exhaled nitric oxide, percutaneous skin testing results to aeroallergens, peripheral eosinophils, serum IgE levels, and serum YKL-40 levels. Results Compared with adults, children with severe persistent asthma had significantly lower YKL-40 levels, higher values for forced vital capacity and forced expiration volume in 1 second, higher serum IgE levels, and higher exhaled nitric oxide levels. YKL-40 levels did not correlate with increasing asthma severity in the pediatric cohort. Conclusion Severe persistent asthma in childhood is not associated with elevated YKL-40 levels, unlike in adults with severe persistent asthma. YKL-40 is not a useful biomarker for asthma severity in childhood asthma.
    Annals of Allergy, Asthma & Immunology. 01/2014;
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    ABSTRACT: For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking. We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%. A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005). Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.)
    New England Journal of Medicine 03/2010; 362(11):975-85. · 54.42 Impact Factor
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    ABSTRACT: The course of mild to moderate persistent asthma in children is not clearly established. To determine the rate and predictors for remitting, periodic, and persistent asthma in adolescence. The Childhood Asthma Management Program (CAMP) was a 4.3-year randomized, double-masked, multicenter trial in children with mild to moderate persistent asthma that compared continuous therapy with either budesonide or nedocromil, each to placebo, followed by a 4-year observational follow-up period. Asthma activity during the observation period included remitting (no asthma activity in the last year), persistent (asthma activity in every quarter), and periodic asthma (neither remitting nor persistent). Asthma was identified as remitting in 6%, periodic in 39%, and persistent in 55% of the 909 participants, with no effect noted from earlier anti-inflammatory treatment during the CAMP trial. Within all 3 asthma activity categories, improvements in airway hyperresponsiveness, eosinophilia, and asthma morbidity were observed over time. Features at entry into CAMP associated with remitting versus persistent asthma were lack of allergen sensitization and exposure to indoor allergens (odds ratio [OR], 3.23; P < .001), milder asthma (OR, 2.01; P = .03), older age (OR, 1.23; P = .01), less airway hyperresponsiveness (higher log methacholine FEV(1) PC(20) (OR, 1.39; P = .03), higher prebronchodilator FEV(1) percent predicted (OR, 1.05; P = .02), and lower forced vital capacity percent predicted (OR, 0.96; P = .04). Remission of asthma in adolescence is infrequent and not affected by 4 years of anti-inflammatory controller therapy. Factors such as sensitization and exposure, low lung function, and airway greater hyperresponsiveness decrease the likelihood of remitting asthma.
    The Journal of allergy and clinical immunology 02/2010; 125(2):359-366.e3. · 12.05 Impact Factor
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    ABSTRACT: Asthma exacerbations occur year-round; however, peak asthma-related events occur in the fall and are frequently associated with viral respiratory infections. To compare the rates of asthma-related emergency department (ED) visits and hospitalizations in the fall (September, October, November) between users and nonusers of fluticasone propionate plus salmeterol in a single inhaler (FSC) in the preceding summer. This was a retrospective, observational study using health care claims from a large managed care database. Patients age 4 to 55 years with both a medical claim for asthma and a pharmacy claim for FSC were categorized into 3 age groups: children (4-11 years), adolescents (12-18 years), and adults (19-55 years). There were 201,973 observations of FSC dispensings and 184,143 observations without FSC. Across all age groups, summertime dispensings of FSC were associated with a significantly lower (P < .001) risk of an asthma-related ED visit (4-11 years: adjusted odds ratio [OR], 0.54, 95% CI, 0.49-0.60; 12-18 years: OR, 0.59, 95% CI, 0.54-0.64; 19-55 years: OR, 0.53, 95% CI, 0.51-0.55) or hospitalization (4-11 years: OR, 0.43, 95% CI, 0.35-0.54; 12-18 years: OR, 0.49, 95% CI, 0.40-0.60; 19-55 years: OR, 0.61, 95% CI, 0.57-0.65) in the subsequent fall. This protective effect persisted even for patients with fall dispensings of FSC. The risk of oral corticosteroid dispensing in the fall was also significantly reduced in all age groups. Summertime dispensings of FSC were associated with a decreased risk of serious asthma-related outcomes in the subsequent fall. Continuous use of FSC before seasonal viral exposure may decrease seasonally related exacerbations.
    The Journal of allergy and clinical immunology 11/2009; 124(6):1197-203. · 12.05 Impact Factor
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2009; 123(2).
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    ABSTRACT: Weak and inconsistent correlations between measurements of asthma health status suggest that the disease is composed of nonoverlapping components. Factor analysis was used to explore the relationships between measures of asthma morbidity and to identify heterogeneous components of asthma health status in children 5 to 12 years old. Results were compared across time (baseline and 48-month visit) and treatment arms. Analyses were conducted in 7 different study windows in a database from a large clinical trial of children with mild to moderate asthma (n = 1041). Measurements of lung function, symptoms, and health care utilization from daily diary cards, serum IgE levels, total eosinophil count, skin test positivity, and airway hyperresponsiveness were included. Data on fractional exhaled nitric oxide and sputum eosinophil cationic protein were included in a subgroup of patients. In each of the study windows, factor analysis identified 5 factors that explained between 50% and 60% of the common variance. Factors identified included (1) inflammatory markers, (2) symptoms/medication use, (3) asthma exacerbations, and measures of lung function, which subdivided into (4) FEV(1) and forced vital capacity, and (5) bronchodilator response and the FEV(1)/forced vital capacity ratio. Exploratory analyses suggest that fractional exhaled nitric oxide account for the atopy/inflammatory marker factor, and sputum measurements account for a sixth, separate factor. The consistent identification of a 5-factor structure across time and treatment arms suggests that each of these factors provides independent information in the assessment of asthma.
    The Journal of allergy and clinical immunology 06/2008; 121(5):1175-80. · 12.05 Impact Factor
  • Joseph D Spahn, Ronina Covar
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    ABSTRACT: Asthma is a heterogeneous disorder with a variable course, characterized by episodes of cough, wheezing and shortness of breath, reversible airflow limitation, and bronchial hyperresponsiveness. It begins early in life in many subjects with intermittent symptoms occurring with viral respiratory tract infections. Over time, and in genetically susceptible children (those with an atopic predisposition), the disease becomes more persistent with symptoms occurring in the absence of respiratory tract infections. Children with persistent wheezing are eventually diagnosed with asthma, with those at greatest risk having developed allergic sensitization early in life. Among children with asthma, some will have lifelong asthma with active symptoms and progressive loss of lung function over time, whereas other children will undergo asthma remission in adolescence. Once in remission, the disease may remain quiescent, or it may relapse in midadult life. This review focuses on studies that have enhanced our understanding of the progression of asthma from infancy to adulthood. Studies evaluating progressive loss of lung function, the best-studied measure of asthma progression, are also reviewed, followed by a brief discussion of whether asthma progression can be modified by inhaled glucocorticoid therapy.
    The Journal of allergy and clinical immunology 04/2008; 121(3):548-57; quiz 558-9. · 12.05 Impact Factor
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2008; 121(2).
  • J. Spahn, J. Doshi, E. Brown, R. Covar
    Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2008; 121(2).
  • Joseph D. Spahn, Ronina Covar
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    ABSTRACT: Glucocorticoids (GCs) are the most effective therapy we have for the treatment of asthma. Systemically administered GCs are first-line agents for acute severe asthma, whereas topical (i.e., inhaled) GCs are first line agents for the long-term management of all patients with persistent asthma. In the treatment of acute asthma exacerbations, early institution of systemic GCs can prevent further worsening of symptoms, reduce emergency room visits, and hospitalizations. Inhaled GCs are the recommended controller class of medications for all patients with persistent asthma, including children. They are the most effective class of agents in reducing symptoms, improving lung function, and decreasing bronchial hyperresponsiveness, in addition to reducing asthma morbidity and mortality. Long-term administration of oral GCs is associated with multiple adverse effects including adrenal insufficiency, weight gain, increased skin fragility, myopathy, osteoporosis, cataracts, and mood changes. Thus, in patients with chronic severe asthma who require regular systemic GC therapy, all other treatments should be maximized, and the lowest dose sufficient for control should be established through regular monitoring visits. As with oral GC therapy, high-dose inhaled GC therapy can result in systemic adverse effects. Several studies have shown that low-dose inhaled GC therapy, even when administered long term, is unlikely to result in any clinically meaningful adverse effects. By using the lowest possible effective GC dose, as well as maximizing other therapeutic modalities, adverse systemic effects from GCs can be greatly minimized.
    12/2007: pages 385-401;
  • Joseph D Spahn
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    ABSTRACT: Several inflammatory cells are thought to contribute to the pathogenesis of asthma. Among these, the eosinophil appears to be a major effector cell. This review focuses primarily on the clinical utility of sputum eosinophil counts in asthma. Several studies have shown sputum eosinophils to be associated with both asthma severity and level of asthma control. In addition, the presence of sputum eosinophilia is strongly predictive of a favorable response to glucocorticoid therapy. Conversely, the absence of sputum eosinophilia is predictive of a poor response to glucocorticoid therapy. Sputum eosinophilia also predicts asthma relapse in subjects who have their inhaled glucocorticoid reduced or withdrawn. Lastly, inhaled glucocorticoid therapy can be titrated to keep the sputum eosinophil count at or below 2%.
    Immunology and Allergy Clinics of North America 12/2007; 27(4):607-22; vi. · 2.38 Impact Factor
  • Joseph D Spahn, Stanley J Szefler
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    ABSTRACT: To highlight studies that have contributed significantly to our current knowledge of inhaled glucocorticoids in childhood asthma. In 2006, three important studies were published that investigated whether inhaled glucocorticoid therapy, if started soon after the onset of asthma symptoms, could alter the subsequent course of the disease. Several studies focused on the comparative clinical efficacy of inhaled glucocorticoids to leukotriene receptor antagonists in children with mild to moderate asthma. Although the Expert Panel had recommended inhaled glucocorticoid therapy as the preferred long-term controller with persistent asthma, there were no specific studies comparing these two classes of long-term controller medications in children. Another topic of significant clinical interest was the comparative efficacy of inhaled glucocorticoid to systemic glucocorticoids in the treatment of acute asthma. The question was answered in a study published in children with mild to moderate acute asthma. Lastly, the safety of inhaled glucocorticoid therapy was also evaluated in preschool children. Inhaled glucocorticoids are the preferred long-term controller for initiating treatment of persistent asthma. Early intervention with inhaled glucocorticoids achieves symptom control but does not alter the natural history of asthma. Inhaled glucocorticoids are not as effective as systemic glucocorticoids for managing acute asthma exacerbations.
    Current Opinion in Pediatrics 07/2007; 19(3):300-5. · 2.63 Impact Factor
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    ABSTRACT: More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children. The Pediatric Asthma Controller Trial (PACT) compared the effectiveness of 3 regimens in achieving asthma control. A total of 285 children (ages 6-14 years) with mild-moderate persistent asthma on the basis of symptoms, and with FEV(1) >or= 80% predicted and methacholine FEV(1) PC(20) <or= 12.5 mg/mL, were randomized to 1 of 3 double-blind 48-week treatments: fluticasone 100 microg twice daily (fluticasone monotherapy), fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening (PACT combination), and montelukast 5 mg in the evening. Outcomes included asthma control days (primary outcome), exacerbations, humanistic measurements, and pulmonary function measurements. Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes, including percent of asthma control days, but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity (P = .015), maximum bronchodilator response (P = .009), exhaled nitric oxide (P < .001), and PC(20) (P < .001). Fluticasone monotherapy was superior to montelukast for asthma control days (64.2% vs 52.5%; P = .004) and for all other control outcomes. Growth over 48 weeks was not statistically different (fluticasone, 5.3 cm; PACT combination, 5.3 cm; montelukast, 5.7 cm). Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast. However, fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control. Growth was similar in all groups. Therefore, of the regimens tested, the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1) >or= 80% predicted, confirming current guideline recommendations.
    Journal of Allergy and Clinical Immunology 01/2007; 119(1):64-72. · 12.05 Impact Factor
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    Bradley E Chipps, Joseph D Spahn
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    ABSTRACT: The evolution of our understanding of treatment of asthma begins with assessment of severity which is primarily related to the natural history of the disease. Control is defined as normalizing of the physiologic abnormalities and lessening economic and social burden of the disease. This paper reviews the factors that influence the variability and determinants of asthma control. The tools to validate and access asthma control should be employed in daily clinical practice. Therefore, it is important to determine asthma control based on a multidimensional approach including physiologic assessment, global assessment of functionality, daytime symptoms, nighttime symptoms, healthcare utilization, and adherence to therapy.
    Journal of Asthma 11/2006; 43(8):567-72. · 1.85 Impact Factor
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    ABSTRACT: We conducted a national, population-based survey to examine the asthma-related health burden of US children. A telephone-based survey was conducted in 2004 of children 4 to 18 years of age with current asthma in the United States. In 41,433 households screened, 1089 children reported current asthma; 801 interviews were completed by parents of children aged 4 to 15 years and by children themselves aged 16 to 18 years. The survey included questions about symptoms, perceived level of control, activity limitations, health care use, medicines, disease management, and knowledge. Global asthma symptom burden, derived from the National Asthma Education and Prevention Program guidelines, was composed of 3 components: short-term symptom burden (4-week recall), long-term symptom burden (past year), and functional impact (activity limitation). The majority of children were classified with mild intermittent disease on the basis of recent daytime symptoms alone (80%); yet, when report of nighttime symptoms was included, the proportion of children classified as having mild intermittent symptoms decreased (74%). When asthma burden was assessed on the basis of the global symptom burden construct, only a minority (13%) of individuals was classified as having an asthma symptom burden consistent with mild intermittent disease; the majority (62%) was classified as having moderate/severe disease. In addition, the impact of asthma on the daily activities is substantial; avoiding exertion (47%) and staying inside (34%) are common approaches to improve control of asthma symptoms. The goals of therapy for asthma, based on the National Asthma Education and Prevention Program guidelines, have not been achieved for the majority of children. In addition, parents and children overestimate the child's asthma control and commonly restrict activities to control asthma symptoms. Deficiencies in the control of asthma may be related to the underestimation of the burden of disease.
    PEDIATRICS 09/2006; 118(2):619-25. · 4.47 Impact Factor
  • Joseph D Spahn, Andrew H Liu
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 07/2006; 96(6):759-61. · 3.45 Impact Factor
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    ABSTRACT: To compare the resource utilization and healthcare costs of children with a diagnosis of asthma, children dispensed asthma medications but without a diagnosis of asthma, and control children. Children 0 to 17 years old were identified from an integrated managed-care database during calendar year 2001. They were compared on the basis of the presence of a medical claim for asthma (Dx cohort); a prescription for an asthma controller or reliever medication (excluding oral corticosteroids) but without an asthma diagnosis (Rx cohort), and control children. Using medical and pharmacy claims, resource utilization and costs were compared across cohorts. Children in both the Dx and Rx cohorts had significantly greater nonasthma and total all-cause annual healthcare costs compared with control children. The Dx and Rx cohorts had higher rates of nonasthma emergency department visits and hospitalizations. The risk of an oral corticosteroid dispensed was 14-fold and 7-fold greater for the Dx and Rx cohorts, respectively, compared with the control children. These findings were consistent in infant, toddler, school-age, and adolescent groups. Children dispensed asthma medications but lacking an asthma diagnosis have considerable morbidity and incur high healthcare resource utilization. This study suggests that better recognition of pediatric asthma is warranted.
    Journal of Pediatrics 07/2006; 148(6):819-23. · 4.04 Impact Factor

Publication Stats

2k Citations
539.50 Total Impact Points

Institutions

  • 2010
    • Johns Hopkins Bloomberg School of Public Health
      Baltimore, Maryland, United States
  • 2007–2010
    • University of Wisconsin, Madison
      • Department of Pediatrics
      Madison, MS, United States
  • 2003–2010
    • National Jewish Health
      • Department of Pediatrics
      Denver, Colorado, United States
  • 2006
    • University of California, San Diego
      • Department of Pediatrics
      San Diego, CA, United States
  • 2002–2006
    • University of Colorado
      • • Department of Pediatrics
      • • Department of Medicine
      Denver, Colorado, United States
  • 2005
    • Texas Tech University Health Sciences Center
      • Department of Pediatrics
      Lubbock, TX, United States
  • 2004
    • National Research Center (CO, USA)
      Boulder, Colorado, United States
  • 2001
    • University of California, San Francisco
      San Francisco, California, United States