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• W2574765746 abstract "Periostin is a matricellular protein upregulated by IL-4 and IL-13 and released by airway epithelial cells. Its levels in peripheral blood are associated with eosinophilic airway inflammation in patients with poorly controlled asthma despite maximal inhaled corticosteroid (ICS) therapy.1Jia G. Erickson R.W. Choy D.F. Mosesova S. Wu L.C. Solberg O.D. et al.Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients.J Allergy Clin Immunol. 2012; 130: 647-654.e10Abstract Full Text Full Text PDF PubMed Scopus (489) Google Scholar High levels of serum periostin in asthmatic patients are associated with higher rates of severe exacerbations and greater FEV1 decrease with time.2Kanemitsu Y. Matsumoto H. Izuhara K. Tohda Y. Kita H. Horiguchi T. et al.Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids.J Allergy Clin Immunol. 2013; 132: 305-312.e3Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar There is also evidence that high serum periostin levels can predict responsiveness to mAb therapy directed against IL-4 receptor subunit alpha,3Wenzel S. Swanson B. Teper A. Hamilton J. Izuhara K. Ohta S. et al.Dupilumab reduces severe exacerbations in periostin-high and periostin-low asthma patients.Eur Respir J. 2016; 48 (1798)Crossref Google Scholar IL-13,4Corren J. Lemanske R.F. Hanania N.A. Korenblat P.E. Parsey M.V. Arron J.R. et al.Lebrikizumab treatment in adults with asthma.N Engl J Med. 2011; 365: 1088-1098Crossref PubMed Scopus (1343) Google Scholar and IgE.5Hanania N.A. Wenzel S. Rosén K. Hsieh H.-J. Mosesova S. Choy D.F. et al.Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study.Am J Respir Crit Care Med. 2013; 187: 804-811Crossref PubMed Scopus (681) Google Scholar To better understand the profile of periostin as a biomarker in asthmatic patients, we have recently defined the reference ranges of periostin in a population of adults with asthma6Fingleton J. Braithwaite I. Travers J. Bowles D. Strik R. Siebers R. et al.Serum periostin in obstructive airways disease.Eur Respir J. 2016; 47: 1383-1391Crossref PubMed Scopus (30) Google Scholar and a population of adults without asthma or chronic obstructive pulmonary disease.7Caswell-Smith R. Hosking A. Cripps T. Holweg C. Matthews J. Holliday M. et al.Reference ranges for serum periostin in a population without asthma or chronic obstructive pulmonary disease.Clin Exp Allergy. 2016; 46: 1303-1314Crossref PubMed Scopus (0) Google Scholar These studies suggest that periostin is not a measure that can usefully discriminate between patients with asthma across a range of severities or from a population without asthma or chronic obstructive pulmonary disease. A characteristic that would need to be established if periostin is to be used as a biomarker in asthmatic patients is its short-term variability in patients with stable asthma. The objective of this study was to determine the variation in serum periostin levels in adults with stable asthma receiving long-term ICS and long-acting β-agonist (LABA) therapy. We hypothesized that there would be little intraparticipant variation in periostin levels in the absence of an asthma exacerbation. This prospective cohort study recruited 60 adults aged between 18 and 75 years. All participants had a doctor's diagnosis of asthma and were receiving stable treatment regimens of an ICS and LABA. Ethical approval was given by the New Zealand Health and Disability Ethics Committee (13/NTB/185). The trial was prospectively registered with the Australia New Zealand Trial Registry (ACTRN126140000235606). Informed written consent was obtained for all participants. Participants attended the Medical Research Institute of New Zealand (MRINZ) outpatient facility for 11 visits over 8 weeks. There were daily visits for the first 5 days, followed by a sixth visit at day 10, weekly visits for 4 weeks, and a final visit 3 weeks later (for full methodology and study plan, see Table E1 in this article's Online Repository at www.jacionline.org). At baseline, participants answered 3 health questionnaires to determine asthma severity, quality of life, and health status; performed basic spirometry and had fraction of exhaled nitric oxide (Feno) measured; and had venous blood drawn for analysis of full blood counts, serum IgE levels, and serum periostin levels. Venous blood for the measurement of serum periostin was collected at all 11 visits. The Asthma Control Questionnaire (ACQ), scoring asthma severity in the week before data collection, was administered at both baseline and every visit from visits 6 to 11. Spirometry was performed with a MasterScreen Pneumo device (MasterScreen Version 2.0; CareFusion, Hoechberg, Germany). Feno values were measured with a nitric oxide monitor (NIOX MINO; Aerocrine AB, Solna, Sweden), according to American Thoracic Society (ATS) guidelines.8American Thoracic SocietyATS workshop proceedings: exhaled nitric oxide and nitric oxide oxidative metabolism in exhaled breath condensate: executive summary.Am J Respir Crit Care Med. 2006; 173: 811-813Crossref PubMed Scopus (53) Google Scholar Serum periostin levels were determined by using the clinical trial version of the Elecsys periostin immunoassay (Roche Diagnostics, Penzbery, Germany). This assay is an automated electrochemiluminescence immunoassay based on the sandwich principle using the same antibodies reported previously.1Jia G. Erickson R.W. Choy D.F. Mosesova S. Wu L.C. Solberg O.D. et al.Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients.J Allergy Clin Immunol. 2012; 130: 647-654.e10Abstract Full Text Full Text PDF PubMed Scopus (489) Google Scholar Participants were taking a median ICS dose of 500 μg of fluticasone propionate equivalent per day and had well-controlled asthma with a mean FEV1 of 101% of predicted value, a mean ACQ score of 0.89, and a mean Feno value of 24.6 ppb (full participants' characteristics are shown in Table E2 in this article's Online Repository at www.jacionline.org). The range of periostin values was 23.2 to 106.6 ng/mL, with a mean (SD) value of 52.2 ng/mL (16.4 ng/mL) and a median value of 48.9 ng/mL. Individual participant mean periostin levels were ranked and are depicted in Fig 1 (all periostin values per visit are shown in Table E3 in this article's Online Repository at www.jacionline.org). The estimate of interparticipant variance in periostin levels based on the raw-scale measurements was 193.6, which was large in comparison with the intraparticipant variance of 15.3, as shown in sequential Bland-Altman plots in Fig E1 in this article's Online Repository at www.jacionline.org. This is consistent with low variability of periostin levels within subjects in a clinical sample representing a well-controlled adult asthmatic population. The 95% CI for individual predictions of periostin levels were plus or minus 7.7 ng/mL. The mean coefficient of variation for periostin for the 60 participants was 6.3% (95% CI, 5.7% to 7.0%). There was no evidence of monthly (P = .56, see Table E4 in this article's Online Repository at www.jacionline.org) or seasonal (P = .90. see Table E5 in this article's Online Repository at www.jacionline.org) variation between participants. Five participants had a severe asthma exacerbation during the study and required systemic corticosteroids (Fig 2) with a mean dose of 35 mg/d (range, 20-60 mg/d; courses lasting from 1-16 days; see Table E6 in this article's Online Repository at www.jacionline.org). The mixed linear model estimate of the difference in periostin levels between the first measurement after a severe exacerbation requiring systemic corticosteroids and the pre-exacerbation measurements for these 5 participants was −5.4 ng/mL (95% CI, −8.3 to −2.6 ng/mL; P = .002). The difference in periostin levels between the postexacerbation and pre-exacerbation levels was −4.5 ng/mL (95% CI, −7.0 to −1.9 ng/mL [P < .001]; which is smaller than the 95% CI for an individual prediction of periostin levels).Fig 2Joined line plot by time of periostin measurement in the 5 participants with a severe exacerbation requiring prednisone use. The arrow marks the periostin measurement taken after the severe exacerbation requiring prednisone.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In summary, we found little variability in periostin measurements within subjects over an 8-week period. The within-participant variance was 15.3, with a 95% CI for periostin levels of ±7.7 ng/mL. These findings in adults receiving step 4 treatment according to Global Initiative for Asthma guidelines9Pocket guide for asthma management and prevention (for adults and children older than 5 years). Available at: http://www.ginasthma.org/local/uploads/files/GINA_Pocket_April20_1.pdf. Accessed July 25, 2015.Google Scholar are consistent with those of studies performed in populations with severe asthma over a period of 24Corren J. Lemanske R.F. Hanania N.A. Korenblat P.E. Parsey M.V. Arron J.R. et al.Lebrikizumab treatment in adults with asthma.N Engl J Med. 2011; 365: 1088-1098Crossref PubMed Scopus (1343) Google Scholar and 51Jia G. Erickson R.W. Choy D.F. Mosesova S. Wu L.C. Solberg O.D. et al.Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients.J Allergy Clin Immunol. 2012; 130: 647-654.e10Abstract Full Text Full Text PDF PubMed Scopus (489) Google Scholar weeks, respectively. These studies reported a coefficient of variation rather than variance components, with point estimates of 5.0% and 5.3%, respectively. This is consistent with the low intraparticipant variability in periostin measurements observed in this study, in which the coefficient of variation was 6.3%. We found no evidence of a monthly or seasonal fluctuation in serum periostin levels between participants who were recruited over a 12-month period. Therefore it might not be necessary to consider seasonality when assessing periostin levels in candidates for treatment with the novel asthma biologic therapies. Periostin levels are modestly reduced by systemic corticosteroid treatment of a severe asthma exacerbation, but the effect lies within the level of variation expected in otherwise stable adults with asthma. In conclusion, we propose that the stability of periostin measurements supports its use as a biomarker in asthmatic patients, predicting responsiveness to biologic therapy directed against type 2 disease. We thank the study participants for their involvement in this study. This prospective cohort study recruited 60 adults aged between 18 and 75 years from the MRINZ volunteer database and local advertising in the Wellington area. Inclusion criteria were a doctor's diagnosis of asthma and prescription of maintenance ICS and LABA therapy at a stable dose for a minimum of 3 months. Exclusion criteria included scenarios that might reasonably be expected to influence periostin measurement, such as unstable asthma (as determined by the investigator and/or a change in asthma medication within the preceding 3 months), systemic corticosteroid use or hospital admission within 3 months, major surgery requiring general anesthetic, tooth extractions or bone fracture occurring within the preceding 3 months, active (current or within the preceding 3 weeks) upper or lower respiratory tract infection, known pregnancy, significant comorbidity, or any safety concern at the investigator's discretion. After telephone prescreening to assess eligibility to participate in the study, participants attended the MRINZ outpatient facility for a total of 11 visits over 59 days. There were daily visits for the first 5 days, followed by a sixth visit at day 10, weekly visits for 4 weeks, and a final visit 3 weeks later. Study procedures were carried out, as detailed in the study plan (Table E1). Three health questionnaires were administered:I.A general health questionnaire was used to ascertain the current health status of participants, implementing questions from the ATS Division of Lung Diseasees-78 Questionnaire.E1Ferris B.G. Epidemiology Standardization Project (American Thoracic Society).Am Rev Respir Dis. 1978; 118: 1-120PubMed Google ScholarII.The AQLQ(S), a validated 32-question self-administered questionnaire, was used to assess quality of life in the 2 weeks before the first visit.E2Juniper E.F. Guyatt G.H. Epstein R.S. Ferrie P.J. Jaeschke R. Hiller T.K. Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials.Thorax. 1992; 47: 76-83Crossref PubMed Scopus (1024) Google ScholarIII.The ACQ-5 was used to determine asthma severity in the week before visit 1.E3Juniper E.F. Svensson K. Mörk A.-C. Ståhl E. Measurement properties and interpretation of three shortened versions of the asthma control questionnaire.Respir Med. 2005; 99: 553-558Abstract Full Text Full Text PDF PubMed Scopus (646) Google Scholar Spirometry was performed with a MasterScreen Pneumo device (MasterScreen Version 2.0; CareFusion) in accordance with ATS guidelines.E4Miller M.R. Hankinson J. Brusasco V. Burgos F. Casaburi R. Coates A. et al.Standardisation of spirometry.Eur Respir J. 2005; 26: 319-338Crossref PubMed Scopus (11489) Google Scholar Feno values were measured with a nitric oxide monitor (NIOX MINO; Aerocrine AB, Solna, Sweden), according to ATS guidelines.E5American Thoracic SocietyATS workshop proceedings: exhaled nitric oxide and nitric oxide oxidative metabolism in exhaled breath condensate: executive summary.Am J Respir Crit Care Med. 2006; 173: 811-813Crossref PubMed Scopus (61) Google Scholar Full blood counts with white blood cell differential (Sysmex, Aucklandm New Zealand) and serum IgE measurements (Roche Cobas e601) were processed immediately. The remaining blood samples were centrifuged, and serum aliquots were stored at −80°C before analysis of serum periostin levels. Serum periostin levels were determined by using the clinical trial version of the Elecsys periostin immunoassay (Roche Diagnostics). All participants were instructed to continue taking their asthma medication as usual for the duration of the study period. The use of any additional medication or a change to regular medication during the study period was recorded. The sample size of 60 participants was chosen to ensure that even if there was 20% attrition, 50 participants would remain in the study, which would provide very good precision for the estimate of variance. In our past work with periostin, its distribution was right skewed and better treated on the logarithm scale for analysis.E6Fingleton J. Braithwaite I. Travers J. Bowles D. Strik R. Siebers R. et al.Serum periostin in obstructive airways disease.Eur Respir J. 2016; 47: 1383-1391Crossref PubMed Scopus (42) Google Scholar, E7Caswell-Smith R. Hosking A. Cripps T. Holweg C. Matthews J. Holliday M. et al.Reference ranges for serum periostin in a population without asthma or COPD.Clin Exp Allergy. 2016; 46: 1303-1314Crossref PubMed Scopus (32) Google Scholar However, in this group of participants, the distribution was not particularly skewed, and our analyses for limits of agreement are shown both on the raw and log-transformed scale. The exploration of differences between month, season, and exacerbation status is performed on the raw scale. Differences in logarithms, where these are presented, are equivalent with exponentiation to the ratio of geometric means. The intraclass correlation coefficient is the ratio of the between-participant variance to the sum of the between- and within-participant variances. A number close to 1 means most of the variation is between participants. The 95% prediction limits for an individual value is plus or minus the within-participant SD times 1.96 and the 90% limits plus or minus 1.69 times the within-participant SD. To compare our data with those summarized from past research that used the coefficient of variation to illustrate measurement variability, we also calculated the coefficient of variation (SD divided by the mean expressed as a percentage) for each participant and estimated the mean coefficient of variation and a 95% CI for this based on a 1-sample t test. Mixed linear models, as described above, were used to compare months and seasons, treating these as fixed effects. The model-based least squares means for each month and season are also shown because these take into account the repeated measures. A post hoc analysis estimated the change in periostin levels around the time of a severe asthma exacerbation, which we defined as worsening asthma symptoms requiring systemic corticosteroids. There were 5 participants who had a severe exacerbation. For the comparison of periostin levels before, during (defined as while receiving systemic corticosteroids), and after an exacerbation, the mixed linear model described above was used with fixed effects for whether the measurement was made under one of the exacerbation conditions. The overall P value for these analyses examined any evidence of a difference between the 3 time periods in relation to exacerbation. Comparisons were made for the following: periostin levels before versus during an exacerbation, and periostin levels before and after an exacerbation. SAS software (version 9.3; SAS Institute, Cary, NC) was used.Fig E1Sequential Bland-Altman plots depicting limits of agreement, illustrating between-participant variability at consecutive visits compared with baseline levels.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table E1Study designVisit no.:1a1b234567891011Time pointUp to 14 d before day 1Day 1 ± 1 dDay 2 ± 1 dDay 3 ± 1 dDay 4 ± 1 dDay 5 ± 1 dDay 10 ± 1 dDay 17 ± 1 dDay 24 ± 1 dDay 31 ± 1 dDay 38 ± 1 dDay 59 ± 1 dWritten informed consentXEnrollmentXMeasurement of BMIXGeneral health questionnaireXACQ-5XXXXXXXAQLQXPeriostin sampleXXXXXXXXXXXFBC sampleXXXXXXXIgE sampleXFenoXSpirometry (FVC + FEV1)XBMI, Body mass index; FBC, full blood count; FVC, forced vital capacity. Open table in a new tab Table E2Participants' characteristicsContinuous variables (n = 60)Mean (SD)Median (IQR)Minimum-maximumAge (y)49.8 (15.7)48.8 (37.7-63.8)21.0-75.5BMI (kg/m2)28.9 (7.7)27.8 (24.2-32.4)18.30-68.9FEV1 (% predicted)101.5 (13.8)100.4 (92.6-110.2)73.0-129.7ACQ-5 score0.89 (0.88)0.8 (0.1-1.2)0-3.8AQLQ(S) score6.1 (1.0)6.5 (5.8-6.7)2.1-7.0Mean ICS dose (FP equivalent/day)478 (205)500 (400-500)100-1000Eosinophil count (× 109/L)0.27 (0.18)0.20 (0.15-0.30)0-0.8Feno (ppb)24.6 (16.6)19.0 (13.0-29.5)5.0-75.0Logarithm Feno (ppb)3.0 (0.62)2.94 (2.56-3.38)1.61-4.33Periostin (ng/mL)52.2 (16.4)48.9 (41.6-60.3)23.2-106.6Logarithm periostin (ng/mL)3.91 (0.30)3.89 (3.73-4.10)3.15-4.67Categorical variables (n/60)Female sex34 (56.7)Ethnicity European48 (80) Maori5 (8.3) Pacific2 (3.3) Asian3 (5) Other2 (3.3)Current smoker4 (6.7)Other atopy46 (76.7)AQLQL(S), Standardized asthma quality of life questionnaire; BMI, body mass index; FP, fluticasone propionate; IQR, interquartile range. Open table in a new tab Table E3Periostin measurements by participant and day (visit day 1 is the baseline measurement)IDVisit day, serum periostin (ng/mL)12345101724313859135.7736.5436.5138.3236.7244.6436.5538.8735.8143.5336.16260.5761.5664.0462.4162.1461.8154.6456.2662.2559.20NA343.7041.4043.0443.1442.4542.2439.8941.850.244.5247.18458.3055.3954.8454.3954.7760.8857.3550.0951.0656.6351.82552.5449.9049.1547.1643.0746.5350.2648.6348.4740.4650.10637.3741.2639.1440.0138.1240.5537.9436.2241.8643.1839.37788.3185.67NA92.5192.4373.6266.0591.6390.1179.8768.07838.6636.0435.1336.4834.4835.6537.6835.5437.4041.0638.469103.2095.2490.69100.6085.3679.7777.0974.8274.7880.7177.731046.3146.0544.6443.1745.3040.5538.5841.3340.5342.4342.361128.4228.1228.1426.8425.8328.1427.7828.2327.9227.3324.081248.5652.9948.7745.8652.0050.3449.3252.7250.4543.9445.661340.5940.4238.1342.7238.8438.1735.3036.2735.2338.3934.701440.3035.5738.8141.2738.6138.8839.2441.3840.0136.4238.571549.2650.8054.2754.0153.8553.4048.6252.1253.5754.0950.871624.8723.5922.8722.4023.6120.6825.8921.6222.21NA25.961766.2459.5263.8470.9656.84NA66.2582.2760.4057.5852.671851.1256.3352.4952.9252.7053.1352.1550.0352.6452.4350.691941.9747.4943.9542.8843.9239.5444.9743.5140.1341.1546.482037.9035.3338.8442.0038.9138.1434.6138.0136.0035.6239.382160.1056.7851.7951.0152.3851.7353.2157.4258.1155.7956.382272.2666.8171.9769.8270.5173.4969.3970.2575.0562.6861.362336.4437.2939.9836.541.2739.5339.9540.0637.9934.0440.642454.2656.4754.3254.9955.1658.7254.6146.5953.5357.253.832541.9844.0039.0140.9241.4539.0847.1444.0243.1642.8347.072664.2956.4857.1060.6263.0263.3668.2965.8778.7671.5764.462746.1550.5146.7246.6243.9348.7047.4553.9745.8647.7144.552867.3258.3451.1750.7551.0155.8859.4857.2956.6750.8153.752947.4044.9144.3843.0844.4443.6147.2344.1947.7647.2149.653068.5764.360.0570.3869.0065.8257.0067.4363.8762.2664.942867.3258.3451.1750.7551.0155.8859.4857.2956.6750.8153.752947.4044.9144.3843.0844.4443.6147.2344.1947.7647.2149.653068.5764.3060.0570.3869.0065.8257.0067.4363.8762.2664.943152.3452.3851.5650.3054.2454.6353.3753.8550.2452.2050.793245.4148.2346.3747.9746.0748.1945.2549.5545.5046.7946.753353.6349.7550.7747.8952.7251.0850.2452.0952.4448.6251.073457.1759.2455.2352.4450.3356.2654.39NA55.4462.1458.683547.3751.8049.3151.3549.0349.4851.7049.3550.5646.7347.783661.8657.1758.7557.6658.2053.7356.6259.5059.3255.8450.343771.8262.9163.5664.5465.4167.1777.1366.8261.3474.6167.143862.8262.1857.0663.3761.0362.6057.5058.2665.8859.5260.3539106.60107.0097.4292.4599.74102.7094.9294.70102.889.3193.694023.2325.2725.0623.4024.0824.8325.5820.8217.7718.3822.194178.8171.1768.0171.5169.9979.1765.8471.4275.2271.2969.054233.9936.8535.1635.8336.5937.5938.3333.4832.2837.3233.524346.8144.3343.1441.8244.1442.9144.8942.2046.3942.8042.194450.3549.0847.6448.7751.5752.8049.4245.9647.9049.0553.284548.5846.5840.4741.2639.3639.4640.3841.2438.0138.3440.234641.1540.8441.5540.0740.4742.9336.2941.6844.4443.3537.864745.5446.3944.3447.9851.0452.1648.8645.4445.6049.4644.984847.3144.8242.6842.9742.7643.2044.5535.9043.7842.4942.084950.8547.4052.6048.8047.3355.5852.46NA50.0254.1154.985038.1238.4035.4834.5135.3537.0839.0235.9136.3336.7034.575128.7328.1027.9229.0431.4731.7327.1223.7625.5131.4029.465244.1745.0248.4448.9350.0952.7651.4558.0156.8143.5447.765358.2965.7458.4056.2755.7859.7661.5559.5262.9459.0157.765435.3636.5134.5533.7735.4833.5534.9134.3432.4032.4934.555555.2553.3154.9151.5950.6046.3747.4150.7452.0249.8653.495655.0361.2559.7159.9566.7854.3357.8360.2054.5553.5554.545769.7673.6668.9668.1264.9958.6464.3366.0861.7966.3470.575845.1448.4549.6454.5255.59NA53.28NANANANA5957.3257.3354.8758.3655.5253.1755.7852.5959.5052.5450.646064.0162.7455.8650.1847.9445.0348.7448.9853.7751.5959.75 Open table in a new tab Table E4Least squares mean estimates for periostin levels (in nanograms per milliliter) by monthMonthLeast squares mean estimate (95% CI)January50.1 (46.1-54.1)February49.6 (45.6-53.6)March49.3 (45.3-53.4)April50.5 (46.4-54.7)May51.3 (46.9-55.6)June50.8 (46.3-55.2)July49.8 (45.4-54.2)August49.8 (45.0-54.6)September49.8 (45.4-54.2)October50.6 (46.5-54.7)November51.6 (47.5-55.6)December51.0 (46.9-55.1) Open table in a new tab Table E5Least squares mean estimates for periostin (in nanograms per milliliter) by seasonSeasonLeast squares mean estimate (95% CI)Autumn50.3 (46.6-54.1)Winter49.8 (45.8-53.8)Spring50.7 (47.0-54.5)Summer50.3 (46.6-54.0) Open table in a new tab Table E6Participants with severe asthma exacerbationsParticipant no.Dose (prednisone)Course duration120 mg1 d240 mg6 d360 mg8 d420 mg16 d540 mg5 d Open table in a new tab BMI, Body mass index; FBC, full blood count; FVC, forced vital capacity. AQLQL(S), Standardized asthma quality of life questionnaire; BMI, body mass index; FP, fluticasone propionate; IQR, interquartile range." @default.
• W2574765746 created "2017-01-26" @default.
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• W2574765746 date "2017-05-01" @default.
• W2574765746 modified "2023-10-14" @default.
• W2574765746 title "Longitudinal variation of serum periostin levels in adults with stable asthma" @default.
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• W2574765746 doi "https://doi.org/10.1016/j.jaci.2016.11.041" @default.
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