Publications by authors named "Kaharu Sumino"

35 Publications

A multistakeholder Delphi consensus core outcome set for clinical trials in moderate-to-severe asthma (coreASTHMA).

Ann Allergy Asthma Immunol 2021 Jul 27;127(1):116-122.e7. Epub 2021 Mar 27.

Center for Medical Technology Policy, Baltimore, Maryland.

Background: Treatments for long-term control of asthma have improved and include a promising but expensive class of biologic therapies. However, the clinical trials evaluating these and other novel treatments have used a variety of different outcomes to evaluate efficacy. The evolution of asthma care calls for a re-examination of outcomes that are most important to patients and other stakeholders.

Objective: To develop a core set of outcomes to be measured in phase 3 and phase 4 clinical drug trials in patients with moderate-to-severe asthma.

Methods: We used a robust and in-depth multistakeholder consensus process bringing together patients, clinicians, regulators, payers, health technology assessors, researchers, and product developers to reach consensus on outcomes. We used a modified Delphi method to reach consensus, an approach adapted from the Core Outcome Measures in Effectiveness Trials Initiative aligned with contemporary methodological standards for core outcome set development.

Results: The following outcomes were included in the final core set: severe asthma exacerbation, change in asthma control, asthma-specific or severe asthma-specific quality of life, asthma-specific hospital stay (ie, >24-hour stays at any level of care) or admission, and asthma-specific emergency department visit.

Conclusion: These 5 outcomes represent a minimum set of core outcomes for use in phase 3 and phase 4 clinical drug trials in moderate-to-severe asthma. Consistent collection of these outcomes as minimum, independent of whether additional heterogeneous primary or secondary outcomes are included, will allow for meaningful comparisons of the effect of asthma therapies across clinical trials.
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http://dx.doi.org/10.1016/j.anai.2021.03.022DOI Listing
July 2021

Safety and effectiveness of bronchial thermoplasty after 10 years in patients with persistent asthma (BT10+): a follow-up of three randomised controlled trials.

Lancet Respir Med 2021 05 29;9(5):457-466. Epub 2021 Jan 29.

Institut Universitaire de cardiologie et de pneumologie, Université Laval, Québec, QC, Canada.

Background: Bronchial thermoplasty is an endoscopic treatment for uncontrolled asthma. Previous randomised clinical trials have shown that bronchial thermoplasty reduces severe exacerbations in people with asthma. However, the long-term efficacy and safety of bronchial thermoplasty beyond 5 years is unknown. The BT10+ study aimed to investigate the efficacy and safety of bronchial thermoplasty after 10 or more years of follow-up.

Methods: BT10+ was an international, multicentre, follow-up study of participants who were previously enrolled in the AIR, RISA, and AIR2 trials and who had 10 or more years of follow-up since bronchial thermoplasty treatment. Data on patient demographics, quality of life, lung function, CT scans (AIR2 participants only), severe exacerbations, and health-care use during the previous year were collected at the BT10+ 10-year outcomes study visit. The primary effectiveness endpoint was durability of the thermoplasty treatment effect, determined by comparing the proportion of participants who had severe exacerbations during the first and fifth years after bronchial thermoplasty treatment with the proportion of participants who had severe exacerbations during the 12-month period before the BT10+ visit. The primary safety endpoint was the absence of clinically significant post-treatment respiratory image changes after bronchial thermoplasty, defined as bronchiectasis or bronchial stenosis as confirmed by pulmonary volumetric high-resolution CT scan at the BT10+ visit (AIR2 participants only). All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03243292. The last patient was enrolled on Dec 11, 2018. The last patient completed follow-up on Jan 10, 2019.

Findings: The BT10+ study enrolled 192 (45%) of the 429 participants who were enrolled in the AIR, RISA, and AIR2 trials. The BT10+ participants comprised 136 who received bronchial thermoplasty (52% of the 260 participants who received bronchial thermoplasty in the original trials), and 56 sham or control participants (33% of 169 from the original trials). 18 (32%) sham or control participants received bronchial thermoplasty after the previous trials concluded. The participants included in BT10+ were followed for 10·8-15·6 years (median 12·1 years) post-treatment. Baseline characteristics were similar between participants enrolled in BT10+ and those not enrolled. Participants treated with bronchial thermoplasty had similar proportions of severe exacerbations at the BT10+ visit (34 [25%] of 136 participants) compared with 1 year (33 [24%] of 135 participants; difference 0·6%, 95% CI -9·7 to 10·8) and 5 years (28 [22%] of 130 participants; difference 3·5%, -6·7% to 13·6) after treatment. Quality of life measurements and spirometry were similar between year 1, year 5, and the BT10+ visit. At the BT10+ study visit, pulmonary high-resolution CT scans from AIR2 participants treated with bronchial thermoplasty showed that 13 (13%) of 97 participants had bronchiectasis. When compared with baseline high-resolution CT scans, six (7%) of 89 participants treated with bronchial thermoplasty who did not have bronchiectasis at baseline had developed bronchiectasis after treatment (5 classified as mild, 1 classified as moderate). Participants treated with bronchial thermoplasty after the original study and participants in the sham or control group also had reductions in severe exacerbations at the BT10+ visit compared with baseline.

Interpretation: Our findings suggest that efficacy of bronchial thermoplasty is sustained for 10 years or more, with an acceptable safety profile. Therefore, bronchial thermoplasty is a long-acting therapeutic option for patients with asthma that remains uncontrolled despite optimised medical treatment.

Funding: Boston Scientific.
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http://dx.doi.org/10.1016/S2213-2600(20)30408-2DOI Listing
May 2021

A randomized, placebo-controlled trial evaluating effects of lebrikizumab on airway eosinophilic inflammation and remodelling in uncontrolled asthma (CLAVIER).

Clin Exp Allergy 2020 12 4;50(12):1342-1351. Epub 2020 Oct 4.

San Francisco Medical Center, University of California, San Francisco, CA, USA.

Background: The anti-interleukin 13 (IL-13) monoclonal antibody lebrikizumab improves lung function in patients with moderate-to-severe uncontrolled asthma, but its effects on airway inflammation and remodelling are unknown. CLAVIER was designed to assess lebrikizumab's effect on eosinophilic inflammation and remodelling.

Objective: To report safety and efficacy results from enrolled participants with available data from CLAVIER.

Methods: We performed bronchoscopy on patients with uncontrolled asthma before and after 12 weeks of randomized double-blinded treatment with lebrikizumab (n = 31) or placebo (n = 33). The pre-specified primary end-point was relative change in airway subepithelial eosinophils per mm of basement membrane (cells/mm ). Pre-specified secondary and exploratory outcomes included change in IL-13-associated biomarkers and measures of airway remodelling.

Results: There was a baseline imbalance in tissue eosinophils and high variability between treatment groups. There was no discernible change in adjusted mean subepithelial eosinophils/mm in response to lebrikizumab (95% CI, -82.5%, 97.5%). As previously observed, FEV increased after lebrikizumab treatment. Moreover, subepithelial collagen thickness decreased 21.5% after lebrikizumab treatment (95% CI, -32.9%, -10.2%), and fractional exhaled nitric oxide, CCL26 and SERPINB2 mRNA expression in bronchial tissues also reduced. Lebrikizumab was well tolerated, with a safety profile consistent with other lebrikizumab asthma studies.

Conclusions & Clinical Relevance: We did not observe reduced tissue eosinophil numbers in association with lebrikizumab treatment. However, in pre-specified exploratory analyses, lebrikizumab treatment was associated with reduced degree of subepithelial fibrosis, a feature of airway remodelling, as well as improved lung function and reduced key pharmacodynamic biomarkers in bronchial tissues. These results reinforce the importance of IL-13 in airway pathobiology and suggest that neutralization of IL-13 may reduce asthmatic airway remodelling.

Clinical Trial Registration: NCT02099656.
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http://dx.doi.org/10.1111/cea.13731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756263PMC
December 2020

Biomarkers of Type 2 Airway Inflammation as Predictors of Loss of Asthma Control During Step-Down Therapy for Well-Controlled Disease: The Long-Acting Beta-Agonist Step-Down Study (LASST).

J Allergy Clin Immunol Pract 2020 Nov - Dec;8(10):3474-3481. Epub 2020 Jul 18.

Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: Biomarkers that can predict loss of asthma control among patients being considered for step-down therapy in well-controlled disease are lacking.

Objective: To evaluate whether baseline biomarkers of type 2 airway inflammation and/or serial measurement of fractional exhaled nitric oxide (Feno) predict loss of asthma control as therapy is stepped down.

Methods: In subanalyses of a multicenter randomized, double-blind, parallel 3-arm trial comparing strategies for step-down therapy in well-controlled asthma (Long-Acting Beta-Agonist Step-Down Study), we assessed whether baseline atopy as determined by serum aeroallergen allergy screening test (Phadiatop), baseline serum eosinophil peroxidase, or baseline or serial Feno measurements during follow-up predicted the time to loss of asthma control among participants. Loss of asthma control was defined in the study protocol. We analyzed these associations in adjusted models including all participants, after testing for interactions with assignment to each of the 3 treatment groups (continuation of stable dose of combination inhaled corticosteroid-long-acting beta-agonist, step-down of inhaled corticosteroid, or discontinuation of long-acting bronchodilator).

Results: Four hundred forty-seven of the 553 Long-Acting Beta-Agonist Step-Down Study participants who were randomized to 1 of 3 treatment arms and had at least 1 biomarker measurement were included in this analysis. At baseline, higher levels of Feno were significantly associated with greater levels of multiallergen IgE levels (P < .001), but not with serum eosinophil peroxidase (P = .742). Among all participants as a group, elevations in baseline biomarkers were not predictive of a higher risk of treatment failure. In addition, Feno levels measured serially at 6-week intervals demonstrated that compared with participants with low levels (<25 parts per billion), those with intermediate (25-50 parts per billion) and high (>50 parts per billion) levels did not have significantly increased likelihood of subsequent treatment failure (hazard ratios, 1.03 [95% CI, 0.59-1.78] and 1.29 [95% CI, 0.65-2.54], respectively). There were no significant interactions of treatment group and baseline biomarkers.

Conclusions: In patients with well-controlled asthma, neither baseline levels of type 2 airway inflammatory biomarkers nor serial measures of Feno are strong predictors of treatment failure.
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http://dx.doi.org/10.1016/j.jaip.2020.06.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026280PMC
May 2021

Reply.

Authors:
Kaharu Sumino

J Allergy Clin Immunol Pract 2020 06;8(6):2121-2122

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, Mo. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.02.044DOI Listing
June 2020

A Pragmatic Trial of Symptom-Based Inhaled Corticosteroid Use in African-American Children with Mild Asthma.

J Allergy Clin Immunol Pract 2020 01 30;8(1):176-185.e2. Epub 2019 Jul 30.

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, Mo.

Background: Symptom-based adjustment (SBA) of inhaled corticosteroids may be an alternative patient-centered approach in which day-to-day inhaled corticosteroid use is adjusted by symptoms and short-acting β-agonist need.

Objective: To evaluate the effectiveness of SBA in the primary care setting.

Methods: We conducted a randomized, open-label, pragmatic equivalence trial in African-American children (6-17 years old) with mild asthma managed by 12 primary care providers (PCPs). A total of 206 participants were randomized to SBA (as-needed beclomethasone 80 μg with rescue short-acting β-agonist) or provider-based guideline-directed adjustment (PBA): maintenance beclomethasone 80 μg/d (6-11 years old), 160 μg/d (12-17 years old), with subsequent guideline-based dose adjustment by PCPs. PCPs implemented both treatment assignments, with outcomes measured by blinded staff. All participants received symptom recognition and albuterol use education from peer educators. Primary outcome was change in asthma control (measured by Asthma Control Test [ACT]/childhood ACT [cACT]) over 12 months.

Results: Participants had adequately controlled asthma (mean ACT or cACT score = 21.6 ± 2.8) at baseline. After 1 year, there was no significant between-group difference in change in ACT scores (SBA - PBA): ACT: -0.88 (95% CI, -2.19 to 0.42), cACT: -0.73 (-2.09 to 0.62), or combined ACT and cACT (P = .10), and was within the predefined statistical clinical equivalence. The proportion with an exacerbation and measures of lung function were similar between groups. Compared with PBA, SBA led to less beclomethasone use (SBA: 526 μg/mo [95% CI, 412-639 μg] vs PBA: 1961 μg/mo [95% CI, 1681-2241]; P < .0001). More parents in the SBA arm felt they were managing their child's asthma.

Conclusions: SBA in African-American children with mild asthma was similar to PBA in asthma control and events when implemented by PCPs with lower inhaled corticosteroid exposure.
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http://dx.doi.org/10.1016/j.jaip.2019.06.030DOI Listing
January 2020

Beyond Respiratory Syncytial Virus and Rhinovirus in the Pathogenesis and Exacerbation of Asthma: The Role of Metapneumovirus, Bocavirus and Influenza Virus.

Immunol Allergy Clin North Am 2019 08 16;39(3):391-401. Epub 2019 May 16.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, 660 Euclid Avenue, Campus Box 8052, Saint Louis, MO 63110, USA. Electronic address:

Respiratory viruses other than rhinovirus or respiratory syncytial virus, including human metapneumovirus, influenza virus, and human bocavirus, are important pathogens in acute wheezing illness and asthma exacerbations in young children. Whether infection with these viruses in early life is associated with recurrent wheezing and/or asthma is not fully investigated, although there are data to suggest children with human metapneumovirus lower respiratory tract infection may have a higher likelihood of subsequent and recurrent wheezing several years after initial infection.
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http://dx.doi.org/10.1016/j.iac.2019.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127190PMC
August 2019

Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate.

J Allergy Clin Immunol 2019 08 11;144(2):416-425.e7. Epub 2019 Mar 11.

Department of Medicine, Brigham and Women's Hospital, Boston, Mass. Electronic address:

Background: Loss of bronchoprotection (LOBP) with a regularly used long-acting β-adrenergic receptor agonist (LABA) is well documented. LOBP has been attributed to β-adrenergic receptor (B2AR) downregulation, a process requiring farnesylation, which is inhibited by alendronate.

Objective: We sought to determine whether alendronate can reduce LABA-associated LOBP in inhaled corticosteroid (ICS)-treated patients.

Methods: We conducted a randomized, double-blind, placebo-controlled, parallel-design, proof-of-concept trial. Seventy-eight participants with persistent asthma receiving 250 μg of fluticasone twice daily for 2 weeks were randomized to receive alendronate or placebo while initiating salmeterol for 8 weeks. Salmeterol-protected methacholine challenges (SPMChs) and PBMC B2AR numbers (radioligand binding assay) and signaling (cyclic AMP ELISA) were assessed before randomization and after 8 weeks of ICS plus LABA treatment. LOBP was defined as a more than 1 doubling dose reduction in SPMCh PC value.

Results: The mean doubling dose reduction in SPMCh PC value was 0.50 and 0.27 with alendronate and placebo, respectively (P = .62). Thirty-eight percent of participants receiving alendronate and 33% receiving placebo had LOBP (P = .81). The after/before ICS plus LABA treatment ratio of B2AR number was 1.0 for alendronate (P = .86) and 0.8 for placebo (P = .15; P = .31 for difference between treatments). The B2AR signaling ratio was 0.89 for alendronate (P = .43) and 1.02 for placebo (P = .84; P = .44 for difference). Changes in lung function and B2AR number and signaling were similar between those who did and did not experience LOBP.

Conclusion: This study did not find evidence that alendronate reduces LABA-associated LOBP, which relates to the occurrence of LOBP in only one third of participants. LOBP appears to be less common than presumed in concomitant ICS plus LABA-treated asthmatic patients. B2AR downregulation measured in PBMCs does not appear to reflect LOBP.
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http://dx.doi.org/10.1016/j.jaci.2019.01.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950766PMC
August 2019

Older age and obesity are associated with increased airway closure in response to methacholine in patients with asthma.

Respirology 2019 07 5;24(7):638-645. Epub 2019 Mar 5.

Pulmonary and Critical Care, University of Vermont Larner College of Medicine, Burlington, VT, USA.

Background And Objective: The reduction of forced expiratory volume in 1 s (FEV ) in response to methacholine challenge in asthma may reflect two components: airway narrowing, assessed by the change in FEV /forced vital capacity (FVC), and airway closure, assessed by the change in FVC. The purpose of this study was to determine the degree and determinants of airway closure in response to methacholine in a large group of asthmatic patients participating in studies conducted by the American Lung Association-Airways Clinical Research Centers (ALA-ACRC).

Methods: We used the methacholine challenge data from participants in five studies of the ALA-ACRC to determine the closing index, defined as the contribution of airway closure to the decrease in FEV , and calculated as %ΔFVC/%ΔFEV .

Results: There were a total of 936 participants with asthma, among whom the median closing index was 0.67 relative to that of a published healthy population of 0.54. A higher closing index was associated with increased age (10-year increments) (0.04, 95% CI = 0.02, 0.05, P < 0.005) and obesity (0.07, 95% CI = 0.03, 0.10, P < 0.001). There was no association between the closing index and asthma control.

Conclusion: Our findings confirm that airway closure in response to methacholine occurs in a large, diverse population of asthmatic participants, and that increased airway closure is associated with older age and obesity. These findings suggest that therapies targeting airway closure may be important in patients with a high closing index.
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http://dx.doi.org/10.1111/resp.13496DOI Listing
July 2019

Caregiver and pediatric provider perspectives on symptom-based inhaled corticosteroid therapy in asthma.

Respir Med 2018 04 5;137:201-205. Epub 2018 Mar 5.

Washington University School of Medicine, Saint Louis, MO, USA. Electronic address:

Objectives: Guidelines recommend that healthcare providers adjust the dose of inhaled corticosteroids (ICS) in asthma patients based on the degree of symptom severity and control. Symptom-based, intermittent ICS therapy (use of ICS together with short acting bronchodilators- symptom-based adjustment: SBA) has been demonstrated to be comparable to guideline-based management by providers in controlled clinical trials. We sought input from African American caregivers and pediatricians on the acceptability and barriers for this alternative management strategy.

Methods: Focus group interviews of caregivers and individual interviews with community providers of African-American children ages 6-17 years with mild-moderate persistent asthma were conducted by trained facilitators to assess perceptions of how asthma affects children and their caregivers, and of SBA as a management strategy. Interview data were transcribed and analyzed using inductive thematic based coding.

Results: Twenty-six parents participated in six focus groups. Fourteen pediatricians were interviewed. Caregivers reported facing financial burden and difficulty with tracking medications. Caregivers and pediatricians were favorable about SBA, citing its potential for decreased use of medications and cost and similarity to actual care provided. Some caregivers voiced concern that SBA would not be as effective as daily ICS. Caregivers suggested that education on symptom recognition and close communication between physician and patient would facilitate the implementation of SBA.

Conclusions: SBA was generally viewed favorably by caregivers and providers of African American children. However, concerns regarding effectiveness of SBA were voiced by both caregivers and providers. Patient education and provider-patient communication is important in implementing this alternative asthma management strategy.
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http://dx.doi.org/10.1016/j.rmed.2018.03.001DOI Listing
April 2018

Recurrent wheezing in children following human metapneumovirus infection.

J Allergy Clin Immunol 2018 07 2;142(1):297-301.e2. Epub 2018 Mar 2.

Washington University School of Medicine in St Louis, St Louis, Mo. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2018.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773053PMC
July 2018

Use of a Remote Inhaler Monitoring Device to Measure Change in Inhaler Use with Chronic Obstructive Pulmonary Disease Exacerbations.

J Aerosol Med Pulm Drug Deliv 2018 06 16;31(3):191-198. Epub 2017 Oct 16.

3 Department of Health Services Research and Development, VA Puget Sound Health Care System , Seattle, Washington.

Background: Remote inhaler monitoring is an emerging technology that enables the healthcare team to monitor the time and location of a patient's inhaler use. We assessed the feasibility of remote inhaler monitoring for chronic obstructive pulmonary disease (COPD) patients and the pattern of albuterol inhaler use associated with COPD exacerbations.

Methods: Thirty-five participants with COPD used an electronic inhaler sensor for 12 weeks which recorded the date and time of each albuterol actuation. Self-reported COPD exacerbations and healthcare utilization were assessed monthly. We used generalized estimating equations with a logit link to compare the odds of an exacerbation day to a nonexacerbation day by the frequency of daily albuterol use.

Results: Average daily albuterol use on nonexacerbation days varied greatly between patients, ranging from 1.5 to 17.5 puffs. There were 48 exacerbation events observed in 29 participants during the study period, of which 16 were moderate-to-severe exacerbations. During the moderate-to-severe exacerbation days, the median value in average daily albuterol use increased by 14.1% (interquartile range: 2.7%-56.9%) compared to average nonexacerbation days. A 100% increase in inhaler use was associated with increased odds of a moderate-to severe exacerbation (odds ratio 1.54; 95% CI: 1.21-1.97). Approximately 74% of participants reported satisfaction with the sensor.

Conclusions: The electronic inhaler sensor was well received in older patients with COPD over a 12-week period. Increased albuterol use captured by the device was associated with self-reported episodes of moderate-to-severe exacerbations.
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http://dx.doi.org/10.1089/jamp.2017.1383DOI Listing
June 2018

Race is associated with differences in airway inflammation in patients with asthma.

J Allergy Clin Immunol 2017 Jul 6;140(1):257-265.e11. Epub 2017 Jan 6.

Department of Medicine, University of Illinois at Chicago, Chicago, Ill.

Background: African American subjects have a greater burden from asthma compared with white subjects. Whether the pattern of airway inflammation differs between African American and white subjects is unclear.

Objective: We sought to compare sputum airway inflammatory phenotypes of African American and white subjects treated or not with inhaled corticosteroids (ICSs; ICS+ and ICS-, respectively).

Methods: We performed a secondary analysis of self-identified African American and white subjects with asthma enrolled in clinical trials conducted by the National Heart, Lung, and Blood Institute-sponsored Asthma Clinical Research Network and AsthmaNet. Demographics, clinical characteristics, and sputum cytology after sputum induction were examined. We used a sputum eosinophil 2% cut point to define subjects with either an eosinophilic (≥2%) or noneosinophilic (<2%) inflammatory phenotype.

Results: Among 1018 participants, African American subjects (n = 264) had a lower FEV percent predicted (80% vs 85%, P < .01), greater total IgE levels (197 vs 120 IU/mL, P < .01), and a greater proportion with uncontrolled asthma (43% vs 28%, P < .01) compared with white subjects (n = 754). There were 922 subjects in the ICS+ group (248 African American and 674 white subjects) and 298 subjects in the ICS- group (49 African American and 249 white subjects). Eosinophilic airway inflammation was not significantly different between African American and white subjects in either group (percentage with eosinophilic phenotype: ICS+ group: 19% vs 16%, P = .28; ICS- group: 39% vs 35%, P = .65; respectively). However, when adjusted for confounding factors, African American subjects were more likely to exhibit eosinophilic airway inflammation than white subjects in the ICS+ group (odds ratio, 1.58; 95% CI, 1.01-2.48; P = .046) but not in the ICS- group (P = .984).

Conclusion: African American subjects exhibit greater eosinophilic airway inflammation, which might explain the greater asthma burden in this population.
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http://dx.doi.org/10.1016/j.jaci.2016.10.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494010PMC
July 2017

Enrolling African-American and Latino patients with asthma in comparative effectiveness research: Lessons learned from 8 patient-centered studies.

J Allergy Clin Immunol 2016 12 24;138(6):1600-1607. Epub 2016 Oct 24.

Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: African-American and Latino patients are often difficult to recruit for asthma studies. This challenge is a barrier to improving asthma care and outcomes for these populations.

Objectives: We sought to examine the recruitment experiences of 8 asthma comparative effectiveness studies that specifically targeted African-American and Latino patients, and identify the solutions they developed to improve recruitment.

Methods: Case report methodology was used to gather and evaluate information on study design, recruitment procedures and outcomes from study protocols and annual reports, and in-depth interviews with each research team. Data were analyzed for themes, commonalities, and differences.

Results: There were 4 domains of recruitment challenges: individual participant, institutional, research team, and study intervention. Participants had competing demands for time and some did not believe they had asthma. Institutional challenges included organizational policies governing monetary incentives and staff hiring. Research team challenges included ongoing training needs of recruitment staff, and intervention designs often were unappealing to participants because of inconveniences. Teams identified a host of strategies to address these challenges, most importantly engagement of patients and other stakeholders in study design and troubleshooting, and flexibility in data collection and intervention application to meet the varied needs of patients.

Conclusions: Asthma researchers may have greater success with recruitment by addressing uncertainty among patients about asthma diagnosis, engaging stakeholders in all aspects of study design and implementation, and maximizing flexibility of study and intervention protocols. However, even with such efforts, engagement of African-American and Latino patients in asthma research may remain low. Greater investment in research on engaging these populations in asthma research may ultimately be needed to improve their asthma care and outcomes.
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http://dx.doi.org/10.1016/j.jaci.2016.10.011DOI Listing
December 2016

Overuse of short-acting beta-agonist bronchodilators in COPD during periods of clinical stability.

Respir Med 2016 07 12;116:100-6. Epub 2016 May 12.

Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.

Background: Overuse of short-acting beta-agonists (SABA) is described in asthma, but little is known about overuse of SABA in chronic obstructive pulmonary disease (COPD).

Methods: Prospective 3-month cohort study of patients with moderate-to-severe COPD who were provided a portable electronic inhaler sensor to monitor daily SABA use. Subjects wore a pedometer for 3 seven-day periods and were asked to complete a daily diary of symptoms and inhaler use. Overuse was defined as >8 actuations of their SABA per day while clinically stable.

Results: Among 32 participants, 15 overused their SABA inhaler at least once (mean 8.6 ± 5.0 puffs/day), and 6 overused their inhaler more than 50% of monitored days. Compared to those with no overuse, overusers had greater dyspnea (modified Medical Research Council Dyspnea Scale: 2.7 vs. 1.9, p = 0.02), were more likely to use home oxygen (67% vs. 29%, p = 0.04), and were more likely to be on maximal inhaled therapy (long-acting beta-agonist, long-acting antimuscarinic agent, and an inhaled steroid: 40% vs. 6%, p = 0.03), and most had completed pulmonary rehabilitation (67% vs. 0%, p < 0.001). However, 27% of overusers of SABA were not on guideline-concordant COPD therapy.

Conclusions: Overuse of SABA was common and associated with increased disease severity and symptoms, even though overusers were on more COPD-related inhalers and more had completed pulmonary rehabilitation. More research is needed to understand factors associated with inhaler overuse and how to improve correct inhaler use.
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http://dx.doi.org/10.1016/j.rmed.2016.05.011DOI Listing
July 2016

Vitamin D Supplementation and the Risk of Colds in Patients with Asthma.

Am J Respir Crit Care Med 2016 Mar;193(6):634-41

13 Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Rationale: Restoration of vitamin D sufficiency may reduce asthma exacerbations, events that are often associated with respiratory tract infections and cold symptoms.

Objectives: To determine whether vitamin D supplementation reduces cold symptom occurrence and severity in adults with mild to moderate asthma and vitamin D insufficiency.

Methods: Colds were assessed in the AsthmaNet VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness) trial, in which 408 adult patients were randomized to receive placebo or cholecalciferol (100,000 IU load plus 4,000 IU/d) for 28 weeks as add-on therapy. The primary outcome was cold symptom severity, which was assessed using daily scores on the 21-item Wisconsin Upper Respiratory Symptom Survey.

Measurements And Main Results: A total of 203 participants experienced at least one cold. Despite achieving 25-hydroxyvitamin D levels of 41.9 ng/ml (95% confidence interval [CI], 40.1-43.7 ng/ml) by 12 weeks, vitamin D supplementation had no effect on the primary outcome: the average peak WURSS-21 scores (62.0 [95% CI, 55.1-68.9; placebo] and 58.7 [95% CI, 52.4-65.0; vitamin D]; P = 0.39). The rate of colds did not differ between groups (rate ratio [RR], 1.2; 95% CI, 0.9-1.5); however, among African Americans, those receiving vitamin D versus placebo had an increased rate of colds (RR, 1.7; 95% CI, 1.1-2.7; P = 0.02). This was also observed in a responder analysis of all subjects achieving vitamin D sufficiency, regardless of treatment assignment (RR, 1.4; 95% CI, 1.1-1.7; P = 0.009).

Conclusions: Our findings in patients with mild to moderate asthma undergoing an inhaled corticosteroid dose reduction do not support the use of vitamin D supplementation for the purpose of reducing cold severity or frequency.
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http://dx.doi.org/10.1164/rccm.201506-1169OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824938PMC
March 2016

Vitamin D Levels Are Unrelated to the Severity of Respiratory Syncytial Virus Bronchiolitis Among Hospitalized Infants.

J Pediatric Infect Dis Soc 2015 Sep 5;4(3):182-8. Epub 2014 Jun 5.

Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics ; and.

Background: Vitamin D deficiency at birth has been reported as a risk factor for respiratory syncytial virus (RSV) lower respiratory tract infection during the first year of life. Limited data are available on whether an infant's vitamin D status is associated with the severity of acute RSV bronchiolitis.

Methods: Infants < 1 year of age and hospitalized with their first episode of RSV bronchiolitis were enrolled into the RSV Bronchiolitis in Early Life II cohort. We investigated the relationships between vitamin D status at enrollment and the following indicators of bronchiolitis severity: duration of hospitalization, lowest oxygen saturation measured during hospitalization, and bronchiolitis severity score.

Results: Among the 145 enrolled infants, the median (quartile 1 [Q1], Q3) serum 25-OH-VitD level was 36.8 (29.8, 42.3) ng/mL, with 14 infants (9.7%) having deficient serum vitamin D levels (25-OH-VitD <20 ng/mL). Vitamin D-deficient infants were younger than infants with 25-OH-VitD ≥ 20 ng/mL (2.8 vs 4.5 months, respectively; P = .04) and were less likely to consume infant's formula (42.9% vs 87.0%, respectively; P < .01). The following indicators of acute bronchiolitis severity did not differ between infants who were vitamin D-deficient and nondeficient: duration of hospitalization (P = .53), lowest oxygen saturation (P = .45), and bronchiolitis severity score (P = .97), even after adjusting for age, and for infant's formula consumption.

Conclusions: Among this cohort of infants that were hospitalized for RSV bronchiolitis, vitamin D status at the time of bronchiolitis was not associated with indicators of acute bronchiolitis severity.
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http://dx.doi.org/10.1093/jpids/piu042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554201PMC
September 2015

Precision Medicine. Personalizing Guidelines to the Provider as Well as the Patient: Making the Juice Worth the Squeeze.

Am J Respir Crit Care Med 2015 Jun;191(12):1345-6

2 Division of Pulmonary and Critical Care Medicine Brigham and Women's Hospital Boston, Massachusetts.

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http://dx.doi.org/10.1164/rccm.201504-0809EDDOI Listing
June 2015

Calcium channel blocker reduces airway remodeling-or does it?

Am J Respir Crit Care Med 2015 Apr;191(8):863-4

1 Division of Pulmonary and Critical Care Medicine Washington University School of Medicine Saint Louis, Missouri and.

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http://dx.doi.org/10.1164/rccm.201502-0322EDDOI Listing
April 2015

Interferon response and respiratory virus control are preserved in bronchial epithelial cells in asthma.

J Allergy Clin Immunol 2014 Dec 9;134(6):1402-1412.e7. Epub 2014 Sep 9.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St Louis, Mo. Electronic address:

Background: Some investigators find a deficiency in IFN production from airway epithelial cells infected with human rhinovirus in asthma, but whether this abnormality occurs with other respiratory viruses is uncertain.

Objective: To assess the effect of influenza A virus (IAV) and respiratory syncytial virus (RSV) infection on IFN production and viral level in human bronchial epithelial cells (hBECs) from subjects with and without asthma.

Methods: Primary-culture hBECs from subjects with mild to severe asthma (n = 11) and controls without asthma (hBECs; n = 7) were infected with live or ultraviolet-inactivated IAV (WS/33 strain), RSV (Long strain), or RSV (A/2001/2-20 strain) with multiplicity of infection 0.01 to 1. Levels of virus along with IFN-β and IFN-λ and IFN-stimulated gene expression (tracked by 2'-5'-oligoadenylate synthetase 1 and myxovirus (influenza virus) resistance 1 mRNA) were determined up to 72 hours postinoculation.

Results: After IAV infection, viral levels were increased 2-fold in hBECs from asthmatic subjects compared with nonasthmatic control subjects (P < .05) and this increase occurred in concert with increased IFN-λ1 levels and no significant difference in IFNB1, 2'-5'-oligoadenylate synthetase 1, or myxovirus (influenza virus) resistance 1mRNA levels. After RSV infections, viral levels were not significantly increased in hBECs from asthmatic versus nonasthmatic subjects and the only significant difference between groups was a decrease in IFN-λ levels (P < .05) that correlated with a decrease in viral titer. All these differences were found only at isolated time points and were not sustained throughout the 72-hour infection period.

Conclusions: The results indicate that IAV and RSV control and IFN response to these viruses in airway epithelial cells is remarkably similar between subjects with and without asthma.
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http://dx.doi.org/10.1016/j.jaci.2014.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261010PMC
December 2014

Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial.

JAMA 2014 May;311(20):2083-91

Boston Children's Hospital, Boston, Massachusetts.

Importance: In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency.

Objective: To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels.

Design, Setting, And Participants: The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized.

Interventions: Oral vitamin D3 (100,000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained.

Main Outcomes And Measures: The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care).

Results: Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2-120.4 µg/d] in the vitamin D3 group vs 126.2 µg/d [95% CI, 117.2-135.3 µg/d] in the placebo group; difference of 14.9 µg/d [95% CI, 2.1-27.7 µg/d]).

Conclusions And Relevance: Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma.

Trial Registration: clinicaltrials.gov Identifier: NCT01248065.
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http://dx.doi.org/10.1001/jama.2014.5052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217655PMC
May 2014

Variability of methacholine bronchoprovocation and the effect of inhaled corticosteroids in mild asthma.

Ann Allergy Asthma Immunol 2014 Apr 5;112(4):354-60.e1. Epub 2014 Feb 5.

Washington University School of Medicine, St Louis, Missouri.

Background: The methacholine challenge test quantifies airway hyper-responsiveness, which is measured by the provocative concentration of methacholine causing a 20% decrease in forced expiration volume in 1 second (PC20). The dose-response effect of inhaled corticosteroids (ICS) on PC20 has been inconsistent and within-patient variability of PC20 is not well established.

Objective: To determine the effect of high- vs low-dose ICS on PC20 and within-patient variability in those with repeated measurements of PC20.

Methods: A randomized, double-masked, crossover trial was conducted in patients with asthma on controller medications with PC20 of 8 mg/mL or lower (n = 64) to evaluate the effect of high-dose (1,000 μg/d) vs low-dose (250 μg/d) fluticasone for 4 weeks on PC20. In addition, the variability of PC20 was assessed in participants who underwent 2 or 3 PC20 measurements on the same dose of ICS (n = 27) over a 4-week interval.

Results: Because there was a significant period effect, dose comparison of the change in PC20 was assessed in the first treatment period. There was no significant difference in the change in PC20 for high- vs low-dose ICS (39% vs 30% increase, respectively; P = .87). The within- and between-participant variances for log PC20 were 0.84 and 0.96, respectively, with an intra-class correlation of 0.53, and 37% of participants had more than 2 doubling dose changes in PC20 in those with repeated measurements.

Conclusion: The effect of ICS on PC20 is not dose dependent at fluticasone levels of 250 and 1,000 μg/d. Interpersonal variability for PC20 is large. A lack of precise measurements should be taken into account when interpreting any change in PC20.
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http://dx.doi.org/10.1016/j.anai.2014.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3987862PMC
April 2014

Patient reminder systems and asthma medication adherence: a systematic review.

J Asthma 2014 Jun 13;51(5):536-43. Epub 2014 Feb 13.

College of Medicine, University of Vermont , Burlington, VT , USA .

Objective: One of the most common reasons for medication non-adherence for asthma patients is forgetfulness. Daily medication reminder system interventions in the form of text messages, automated phone calls and audiovisual reminder devices can potentially address this problem. The aim of this review was to assess the effectiveness of reminder systems on patient daily asthma medication adherence.

Methods: We conducted a systematic review of the literature to identify randomized controlled trials (RCTs) which assessed the effect of reminder systems on daily asthma medication adherence. We searched all English-language articles in Pub Med (MEDLINE), CINAHL, EMBASE, PsychINFO and the Cochrane Library through May 2013. We abstracted data on the year of study publication, location, inclusion and exclusion criteria, patient characteristics, reminder system characteristics, effect on patient adherence rate and other outcomes measured. Descriptive statistics were used to summarize the characteristics and results of the studies.

Results: Five RCTs and one pragmatic RCT were included in the analysis. Median follow-up time was 16 weeks. All of the six studies suggested that the reminder system intervention was associated with greater levels of participant asthma medication adherence compared to those participants in the control group. None of the studies documented a change in asthma-related quality of life or clinical asthma outcomes.

Conclusion: All studies in our analysis suggest that reminder systems increase patient medication adherence, but none documented improved clinical outcomes. Further studies with longer intervention durations are needed to assess effects on clinical outcomes, as well as the sustainability of effects on patient adherence.
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http://dx.doi.org/10.3109/02770903.2014.888572DOI Listing
June 2014

Coexisting chronic conditions associated with mortality and morbidity in adult patients with asthma.

J Asthma 2014 Apr 27;51(3):306-14. Epub 2014 Jan 27.

Department of Medicine, Washington University School of Medicine , Saint Louis, MO , USA .

Objective: Many asthma patients suffer from chronic conditions other than asthma. We investigated the specific contribution of common comorbidities on mortality and morbidity in adult asthma.

Methods: In an observational study of adults with incident asthma identified between 1999 and 2003 using National Veterans Affairs and Centers for Medicare and Medicaid Services encounter databases (n = 25 975, follow-up 3.0 ± 1.7 years), association between 13 most prevalent comorbidities (hypertension, ischemic heart disease (IHD), osteoarthritis, rheumatoid arthritis, diabetes, mental disorders, substance/drug abuse, enlarged prostate, depression, cancer, alcoholism, HIV and heart failure) and four conditions previously associated with asthma (sleep apnea, gastroesophageal reflux disease (GERD), rhinitis and sinusitis) and mortality, hospitalizations and asthma exacerbations were assessed using multivariate regression analyses adjusted for other clinically important covariates.

Results: HIV followed by alcoholism and mental disorders among 18-45-years old, and heart failure, diabetes, IHD and cancer among those ≥ 65 years old were associated with an increased risk of all-cause mortality. Many conditions were associated with increased risk for all-cause hospitalizations, but the increased risk was consistent across all ages for mental disorders. For asthma exacerbations, mental disorder followed by substance abuse and IHD were associated with increased risk among those 18-45 years old, and chronic sinusitis, mental disorder and IHD among those ≥ 65-years old. GERD was associated with decreased risk for asthma exacerbation in all ages.

Conclusions: Many comorbidities are associated with poor outcome in adult asthmatics and their effect differs by age. Mental disorders are associated with increased risk of mortality and morbidity across ages.
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http://dx.doi.org/10.3109/02770903.2013.879881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067514PMC
April 2014

Bronchial thermoplasty: safe for our severe asthma patients?

Ann Allergy Asthma Immunol 2013 Nov 5;111(5):311-2. Epub 2013 Sep 5.

Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, Missouri.

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http://dx.doi.org/10.1016/j.anai.2013.08.010DOI Listing
November 2013

Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma.

J Allergy Clin Immunol 2013 Dec 30;132(6):1295-302. Epub 2013 Aug 30.

Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colo. Electronic address:

Background: Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma.

Objective: We sought to assess the effectiveness and safety of BT in asthmatic patients 5 years after therapy.

Methods: BT-treated subjects from the Asthma Intervention Research 2 trial (ClinicalTrials.govNCT01350414) were evaluated annually for 5 years to assess the long-term safety of BT and the durability of its treatment effect. Outcomes assessed after BT included severe exacerbations, adverse events, health care use, spirometric data, and high-resolution computed tomographic scans.

Results: One hundred sixty-two (85.3%) of 190 BT-treated subjects from the Asthma Intervention Research 2 trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and emergency department (ED) visits and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months before BT treatment (average 5-year reduction in proportions: 44% for exacerbations and 78% for ED visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in years 2 through 5 compared with the first year after BT. Prebronchodilator FEV₁ values remained stable between years 1 and 5 after BT, despite a 18% reduction in average daily inhaled corticosteroid dose. High-resolution computed tomographic scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT.

Conclusions: These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ED visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking inhaled corticosteroids and long-acting β₂-agonists.
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http://dx.doi.org/10.1016/j.jaci.2013.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114404PMC
December 2013

Medication adherence in asthma patients.

Curr Opin Pulm Med 2013 Jan;19(1):49-53

Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.

Purpose Of Review: Although current asthma guidelines stress the importance of assessing and enhancing adherence to asthma treatment, medication adherence rates in asthma patients are consistently low in practice. In this review, we summarize current literature on method of measurement, prevalence, outcome and intervention of medication adherence in asthma patients.

Recent Findings: Nonadherence to prescribed treatment continues to be a frequent problem in patients with asthma even in recent years. Objective measurement of adherence should be implemented whenever possible. Review of pharmacy refill data or electronic monitoring of inhaler actuation may be a preferred method to assess adherence. Educational programmes should be specifically designed to address the unmet need and specific reasons for nonadherence for the target population. Large, well designed clinical trials to assess the efficacy of remote electronic monitoring and reminder systems to improve adherence are needed.

Summary: There is an urgent clinical need for systematic, proven methods to assess and address medication nonadherence in asthma patients.
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http://dx.doi.org/10.1097/MCP.0b013e32835b117aDOI Listing
January 2013

Methacholine challenge test: diagnostic characteristics in asthmatic patients receiving controller medications.

J Allergy Clin Immunol 2012 Jul 1;130(1):69-75.e6. Epub 2012 Apr 1.

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.

Background: The methacholine challenge test (MCT) is commonly used to assess airway hyperresponsiveness, but the diagnostic characteristics have not been well studied in asthmatic patients receiving controller medications after the use of high-potency inhaled corticosteroids became common.

Objectives: We investigated the ability of the MCT to differentiate participants with a physician's diagnosis of asthma from nonasthmatic participants.

Methods: We conducted a cohort-control study in asthmatic participants (n= 126) who were receiving regular controller medications and nonasthmatic control participants (n= 93) to evaluate the sensitivity and specificity of the MCT.

Results: The overall sensitivity was 77% and the specificity was 96% with a threshold PC(20) (the provocative concentration of methacholine that results in a 20% drop in FEV(1)) of 8 mg/mL. The sensitivity was significantly lower in white than in African American participants (69% vs 95%, P= .015) and higher in atopic compared with nonatopic (82% vs 52%, P= .005). Increasing the PC(20) threshold from 8 to 16 mg/mL did not noticeably improve the performance characteristics of the test. African American race, presence of atopy, and lower percent predicted FEV(1) were associated with a positive test result.

Conclusions: The utility of the MCT to rule out a diagnosis of asthma depends on racial and atopic characteristics. Clinicians should take into account the reduced sensitivity of the MCT in white and nonatopic asthmatic patients when using this test for the diagnosis of asthma.
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http://dx.doi.org/10.1016/j.jaci.2012.02.025DOI Listing
July 2012

Antiviral IFN-γ responses of monocytes at birth predict respiratory tract illness in the first year of life.

J Allergy Clin Immunol 2012 May 27;129(5):1267-1273.e1. Epub 2012 Mar 27.

Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.

Background: Viral respiratory tract infections are the leading cause of acute illness during infancy and are closely linked to chronic inflammatory airway diseases later in life. However, the determinants of susceptibility to acute respiratory tract infections still need to be defined.

Objective: We investigated whether the individual variation in antiviral response at birth determines the risk for acute respiratory tract illness in the first year of life.

Methods: We studied 82 children who were enrolled in a birth cohort study of inner-city children with at least 1 parent with allergy or asthma. We cultured cord blood monocytes and assessed IFNG and CCL5 mRNA production at 24 hours after inoculation with respiratory syncytial virus. We also monitored the frequency of acute respiratory tract illness at 3-month intervals and analyzed nasal lavage samples for respiratory tract viruses at the time of illness during the first year.

Results: Respiratory tract infection was reported for 88% of subjects, and respiratory tract viruses were recovered in 74% of symptomatic children. We observed a wide range of antiviral responses in cord blood monocytes across the population. Furthermore, a decrease in production of IFNG (but not CCL5) mRNA in response to respiratory syncytial virus infection of monocytes was associated with a significant increase in the frequency of upper respiratory tract infections (r = -0.42, P < .001) and the prevalence of ear and sinus infections, pneumonias, and respiratory-related hospitalizations.

Conclusion: Individual variations in the innate immune response to respiratory tract viruses are detectable even at birth, and these differences predict the susceptibility to acute respiratory tract illness during the first year of life.
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http://dx.doi.org/10.1016/j.jaci.2012.02.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340511PMC
May 2012
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