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The impact of using different symptom-based exacerbation algorithms in patients with COPD

J.C.A. Trappenburg, A.C. van Deventer, T. Troosters, T.J.M. Verheij, A.J.P. Schrijvers, J-W.J. Lammers, E.M. Monninkhof
European Respiratory Journal 2011 37: 1260-1268; DOI: 10.1183/09031936.00130910
J.C.A. Trappenburg
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  • For correspondence: J.C.A.trappenburg@umcutrecht.nl
A.C. van Deventer
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T. Troosters
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T.J.M. Verheij
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A.J.P. Schrijvers
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J-W.J. Lammers
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E.M. Monninkhof
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    Figure 1–

    Flow chart of included and excluded studies.

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  • Table 1– Characteristics of the 51 included studies
    CharacteristicsStudies
    RCT15 (29)
    Cohort study36 (71)
    Evaluation of a pharmacological compound15 (29)
    Patients median (IQR)109 (78–259)
    Follow-up period months median (range)12 (3–90)
    • Data are presented as n (%), unless otherwise stated. RCT: randomised controlled trial; IQR: interquartile range.

  • Table 2– Overview of exacerbation onset algorithms in the included studies#
    AlgorithmStudies nCriteria for defining onsetConsecutive daysDYSVSPCOWHSTCSFECTFADENA
    Modified Anthonisen32Increase in ≥2 symptoms including 1 major≥2+MaMaMaMiMiMiMi-----
    Modified Anthonisen + fever4Increase in ≥2 symptoms including 1 major≥2MaMaMaMiMiMiMiMi----
    Only major symptoms4Increase in ≥1 symptom≥2§+++---------
    Vijayasaratha 111Graded symptom scale; increase in ≥1 point in 1 major symptom≥2MaMaMaMi--MiMiMi---
    Alvarez-Mon 221Increase in ≥2 symptomsNS++++--------
    Ekberg-Jansson 231≥3 points; major symptom = 2 points, minor = 1 point≥2MiMiMiMa------Mi-
    Van Schayk 241Increase in ≥2 symptoms including 1 majorNSMiMiMaMaMiMiMiMiMiMiMi-
    Sund 251Graded symptom score; increase of ≥1 point for 2 symptoms≥2+++----++--
    Banerjee 261“Increase in symptoms”NS------------
    Calverley 271Graded symptom score, 5 different criteria described¶≥3+--+---+---+
    Casaburi 281Increase in ≥1 symptom≥3+--++---+---
    Dowson 291Increase in ≥2 symptoms≥1+++---------
    Pela 301Graded symptom score; increase in ≥3 pointsNS++++---+----
    Dahl 311Increase in ≥1 symptom≥3+++++-------
    • DY: dyspnoea; SV: sputum volume; SP: sputum purulence; CO: cough; WH: wheezing; ST: sore throat; CS: coryzal symptoms; FE: fever; CT: chest tightness; FA: fatigue; DE: difficulty with expectoration; NA: night-time awakenings; NS: not specified; Ma: major symptom; +: included in the algorithm but no distinction between major and minor symptoms; -: not included in the algorithm; Mi: minor symptom. #: n = 51. ¶: see online supplementary material. +: not specified in three studies. §: not specified in two studies.

  • Table 3– Recovery time, severity classification, data registration, attempts to enhance validity of diary registration, blinded adjudication of exacerbations and handling of missing diary data#
    CriteriaStudies n (%)
    Recovery rules¶
     Not reported15 (29)
     Symptom score back to an individual baseline28 (55)
     Symptom score back to a fixed value1 (2)
     First day not meeting onset criteria6 (12)
     All symptoms resolved1 (2)
    Data registration
     Not reported3 (6)
     Daily written diary cards39 (76)
     Daily electronic diary cards1 (2)
     Telephone consultations+4 (8)
     Clinic visits4 (8)
    Blinded adjudication of exacerbations
     Not reported48 (94)
     Yes3 (6)
    Concurrence with event-based exacerbations
     Not reported12 (24)
     Yes39 (76)
    Severity classification
     Not reported18 (35)
     By symptom count at onset§24 (47)
     By number of major symptoms4 (8)
     By duration§5 (10)
     By healthcare utilisation3 (6)
    Attempts to enhance validity and compliance of diary registrationƒ
     Not reported12 (31)
     Run-in period##2 (5)
     Telephone check##4 (10)
     Clinic visit check24 (62)
     Random home visits1 (3)
    Handling of missing diary data
     Not reported48 (94)
     Multiple imputation2 (4)
     Retrospective interviews1 (2)
    • #: n = 51; ¶: rules to define recovery and/or identify new or recurrent events; +: performed monthly in all studies; §: three studies used a severity classification by symptom count and duration; ƒ: from 39 studies using daily diary cards; ##: two studies combined a run-in period with telephone checks.

  • Table 4– Exacerbation rate, type, severity and concurrence with reported/treated events of exacerbation using four different algorithms
    Symptom algorithmExacerbations# nIncidence exacerbations·person-yr−1 (95% CI)Exacerbations n (% total) (% patients with an exacerbation)Clustering type n (% total)Recovery time daysAnthonisen classificaton n (% total)Total symptom count nConcurrence with reported and treated events
    01>1InitialRelapsedRecurrentIIIIIIReported events n (%)Treated events n (%)Missed admissions¶ n
    1.1191.7 (1.4–2.1)81 (59)25 (18) (45)31 (23) (55)69 (58)13 (11)50 (42)14 (7–22)27 (23)38 (32)54 (45)57 (27–94)62 (52)31 (26)1
    2.1191.7 (1.4 –2.1)81 (59)25 (18) (45)31 (23) (55)69 (58)13 (11)50 (42)14 (7–22)27 (23)38 (32)54 (45)57 (27–94)62 (52)31 (26)1
    3. ≥11321.9 (1.6–2.3)73 (53)30 (22) (47)34 (25) (53)75 (57)14 (11)57 (43)13 (7–22)27 (20)39 (30)66 (50)51 (23–91)62 (47)31 (24)1
    4. ≥2541.5 (0.6–1.0)105 (77)20 (15) (63)12 (8) (37)35 (65)2 (4)19 (35)14 (8–21)27 (50)27 (50)70 (42–125)41 (76)22 (41)5
    • Data are presented as median (interquartile range), unless otherwise stated. The symptom alogrithms are: 1. Modified Anthonisen; 2. Modified Anthonisen+fever; 3. ≥1 major symptom; 4. ≥2 major symptoms. #: relapsed exacerbations excluded (original exacerbation and relapse are considered as the same event); ¶: hospital and emergency room visits missed.

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    • Appendix II
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The impact of using different symptom-based exacerbation algorithms in patients with COPD
J.C.A. Trappenburg, A.C. van Deventer, T. Troosters, T.J.M. Verheij, A.J.P. Schrijvers, J-W.J. Lammers, E.M. Monninkhof
European Respiratory Journal May 2011, 37 (5) 1260-1268; DOI: 10.1183/09031936.00130910

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The impact of using different symptom-based exacerbation algorithms in patients with COPD
J.C.A. Trappenburg, A.C. van Deventer, T. Troosters, T.J.M. Verheij, A.J.P. Schrijvers, J-W.J. Lammers, E.M. Monninkhof
European Respiratory Journal May 2011, 37 (5) 1260-1268; DOI: 10.1183/09031936.00130910
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