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Clinimetric properties of bronchoalveolar lavage inflammatory markers in cystic fibrosis

Michael Fayon, Lisa Kent, Stephanie Bui, Lieven Dupont, Isabelle Sermet on behalf of the European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) Standardisation Committee
European Respiratory Journal 2014 43: 610-626; DOI: 10.1183/09031936.00017713
Michael Fayon
1Centre Hospitalier Universitaire de Bordeaux, Hôpital Pellegrin-Enfants, CRCM Pédiatrique, Centre d’Investigation Clinique (CIC 0005), Bordeaux
5Both authors contributed equally
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  • For correspondence: michael.fayon@chu-bordeaux.fr
Lisa Kent
2Institute for Nursing and Health Research, University of Ulster, Belfast, UK
5Both authors contributed equally
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Stephanie Bui
1Centre Hospitalier Universitaire de Bordeaux, Hôpital Pellegrin-Enfants, CRCM Pédiatrique, Centre d’Investigation Clinique (CIC 0005), Bordeaux
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Lieven Dupont
3Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium
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Isabelle Sermet
4Pôle de Pédiatric Multidisciplinaire, INSERM U 845 et Service de Pneumo-Allergologie pédiatrique, Hôpital Necker, Université René Descartes, Paris, France
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  • Table 1– Clinimetric properties of biomarkers
    DefinitionJustification of importance
    ReliabilityDegree to which a measurement is consistent and free from errorImportant to quantify error (systematic and random) so that true changes can be discerned from changes due to normal fluctuations
    ValidityThe gold standard outcome measures are often not feasible; therefore, it is important to know how an alternative outcome measure compares to the gold standard, and how different outcome measures compare It is important to know the ability of outcome measures to discriminate between different groups
     Concurrent validityDegree to which a test correlates with a “gold standard” criterion test which has been established as a valid test of the attribute of interest
     Convergent validityDegree to which a test correlates with another test which measures the same attribute
     Discriminate validityDegree to which a test differentiates between groups of individuals known to differ in the attribute of interest
     Predictive validityDegree to which an attribute can be predicted using the result of a predictor test/or degree to which prognosis can be predicted
    ResponsivenessDegree to which a test changes in response to an intervention known to alter the attribute of interestImportant attribute of tests used in clinical practice or research to assess treatment benefit (e.g. to identify improvements in response to an intervention)
    • Reproduced from [1] with permission.

  • Table 2– Discriminate validity of bronchoalveolar lavage (BAL) inflammatory markers between cystic fibrosis (CF) patients and non-CF subjects
    First author [ref.]Aliquot fraction analysedCFNon-CFPMN cell counts ×10 3 cells·mL−1, unless otherwise statedPMN cells %Neutrophil elastaseIL-6 ×103·mL−1, unless otherwise statedIL-8 ×103·mL−1, unless otherwise statedStatistical testsData presentation
    Subjects nAgeSubjects nAge
    Armstrong [26]F50 infected19.1 (1.5–71) months1912.4±11.8 monthsCF 50 (39–65) versus non-CF 8.2 (4.6–15)***CF 80 (66–90) versus non-CF 32 (13–57)***CF 1153 (754–1762) versus non-CF 24 (12–47)***CF 50 (39–65) versus non-CF 8.2 (4.6–15)***Wald testGeometric mean (95% CI)
    Armstrong [26]F28Infants (age not reported)10Infants (age not reported)CF 11 (8.7–13) versus non-CF 2.1 (0.95–4.7) μg·mL−1***Wald testGeometric mean (95% CI)
    Muhlebach [38]Not specified1725±4 months2515±3 monthsCF 41.2±7.0 versus non-CF 21.8±5.2*CF 6868±2065 pg·mL−1 versus non-CF 1434±362 pg·mL−1¶CF 41.2±7.0 versus non-CF 21.8±5.2*Mann–Whitney U-testMean±sem
    Armstrong [39]F5 virus infectedInfants
    (age not reported)
    13Infants
    (age not reported)
    CF 169 (16–1809) versus non-CF 7 (2–22)***CF 1372 (561–3358) versus non-CF 32 (12–84)***ANCOVAGeometric mean (95% CI)
    Khan [31]P160.48 (0.08–0.97) years111.02 (0.25–2.7) yearsCF 673.6±367.9 versus non-CF 6.9±1.7+CF 1.18±0.46 μg·mL−1 versus non-CF 0 μg·mL−1§CF 1298±338 pg·mL−1 versus non-CF 92±25 pg·mL−1***Independent t-testMean±sem
    Kirchner [40]P1610.5 (2–25) months9 (disease)11.7 (3–30) months¶Kruskal–WallisValues not reported
    Muhlebach [41]#,¶Not specified511.8 years (3 weeks–13 years)50 (disease)1.0 years (2 weeks–8.3 years)*******Independent t-testValues not reported
    Muhlebach [42]#Not specified553.7 (0.1–13) years562.1 (0.04–9) years**Independent t-testValues not reported
    Noah [43]P15 (infected)2.4 (0.1–13) years12 (uninfected)1.4 (0.1–8.8) yearsCF 3358 (100–11 520) versus non-CF 10 (1–117)*CF 84 (16–96) versus non-CF 5 (1–51)*CF 56 (17–681) versus non-CF 10 (2–59)*CF 11 614 (1424–71 100) versus non-CF 459 (21–2040)*Kruskal–WallisMedian (range)
    Noah [43]P15 (infected)2.4 (0.1–13) years12 (infected)1.4 (0.1–8.8) yearsCF 3358 (100–11 520) versus non-CF 229 (1–2976)*CF 84 (16–96) versus non-CF 46 (1–93)*nsCF 11 614 (1424–71 100) versus non-CF 1860 (18–6224)*Kruskal–WallisMedian (range)
    MacGregor [44]P396.4±0.7 years386.1±0.6 yearsnsCF 1308.1±56.4 versus non-CF 716±89.9***Mann–Whitney U-testMean±sem
    Hilliard [45]P436.2 (0.3–16.8) years7 (PCD)9.2 (5.7–14.8) yearsnsnsnsNonparametric tests
    Hilliard [45]P436.2 (0.3–16.8) years26 (CRD)4.8 (0.9–15.2) yearsCF 0.7 (0.02–23.97)×106·mL−1 versus non-CF 0 (0–17.91)×106·mL−1 ***CF 201 (100–5000) μm·mL−1 versus non-CF 100 (100–1297) μm·mL−1 ***CF 1340 (31–1760) pg·mL−1 versus 703 (31–1560) pg·mL−1 ***Nonparametric testsMedian (range)
    Hilliard [45]P436.2 (0.3–16.8) years7 (disease control)5.8 (0.3–16.3) yearsCF 0.7 (0.02–23.97)×106·mL−1 versus non-CF 0 (0–0.01)×106·mL−1 ***CF 201 (100–5000) μm·mL−1 versus non-CF 100 (100–100) μm·mL−1 ***CF 1340 (31–1760) pg·mL−1 versus 64 (31–221) pg·mL−1**Nonparametric testsMedian (range)
    Harris [46]F29 (during exacerbation)9.1±12 years126.0±1.4 yearsCF 6.1±0.12 log10 versus 4.9±0.17 log10***CF 68.8±3.6 versus 16.4±3.8***Wilcoxon rank sum testMean±sem
    Dean [37]svBAL, F58 (4–18) years8 (asthma)Adults (age not reported)CF 6618 (1200–11 136) pM versus non-CF 302.4 (48–984) pM*Not reportedMean (range)
    Dean [37]svBAL, F58 (4–18) years6 (PCD)Children (age not reported)CF 6618 (1200–11 136) pM versus non-CF 302.4 (48–984) pM*ƒNot reportedMean (range)
    Reeves [47]Not specified15Children and adolescents128.21±1.22 yearsMann–Whitney U-testValues not reported
    Ratjen [48]F1055–37 years483–15 yearsFirst aliquot
    CF 52±30 versus non-CF 4±5##
    Mann–Whitney U-testMean±sd
    Ratjen [48]P (aliquots 2 and 3)1055–37 years483–15 yearsPooled CF 29±23 versus non-CF 2±3##¶Mann–Whitney U-testMean±sd
    Reeves [49]F1819.6±5.2 years14 (other disease)50.14±10.5 yearsCF 325±81.96 pg·mg−1 versus 125.92±43.95 pg·mg−1 *Independent t-testMean±sem
    McGarvey [6]F (cytology), P (remaining)1122.7±3.8 years9 (mild asthma)24.1±3.9 yearsnsnsANOVA
    11 (healthy)24.3±2.8 years
    Bonfield [33]P2220±2 years1329±6 yearsCF 41±10×106·mL−1 versus non-CF 0.09±0.02×106·mL−1 *CF 60±5 versus non-CF 1±0.3*CF 1.9±0.5 μM versus non-CF 0 μM*p=0.06
    CF 287±104 versus non-CF 0
    CF 32 565±9686 versus non-CF 0*Kruskal–WallisMean±sem
    Konstan [50]P1820±1 years2325±1 yearsCF 38±14 (1–222)×106·mL−1 versus non-CF 0.1±0.04 (0–0.6)×106·mL−1 *Independent t-testMean±sem (range)
    Meyer [35]P14 (exacerbation)17–40 years819–24 yearsCF 51.1±5.2 versus non-CF 0.3±0.4*CF 323±127 nM·min−1·mL−1 versus non-CF 0 nM·min−1·mL−1*Independent t-testMean±sem
    Nakamura [51]Not specified828±2 years729±3 yearsCF 101±26 versus non-CF 0.4±0.3*CF 31±10 versus non-CF 0*CF 35±13 versus non-CF 0*Not reportedMean (range)
    • All four biomarkers are present at higher levels in patients with CF. All samples are BAL, unless otherwise stated. PMN: polymorphonuclear; IL: interleukin; F: first; P: pooled; svBAL: small volume BAL; ns: not significant; PCD: primary ciliary dyskinesia; CRD: chronic respiratory disease. #: [42] includes patients previously reported in [41]; *: p<0.05; **: p<0.01; ***: p<0.001; ¶: p<0.005; +: p=0.002; §: p=0.03; ƒ: p=0.02; ##: p<0.0001.

  • Table 3– Discriminate validity of bronchoalveolar lavage (BAL) inflammatory markers between groups of patients with cystic fibrosis (CF) with different phenotypes
    First author [ref.]Aliquot fraction analysedGroup 1Group 2PMN cell counts ×103 cells·mL−1, unless otherwise statedPMN cells %Neutrophil elastaseIL-6 ×103·mL−1, unless otherwise statedIL-8 ×103·mL−1, unless otherwise statedStatistical testsData presentation
    Subjects nAgeSubjects nAge
    Sly [9]F (microbiology), P (aliquots 2 and 3)48 asymptomaticInfants9 symptomaticInfantsnsGroup 1 14.5 (9.0–27.1) versus Group 2 39.7 (28.3–65.0)#Group 1 100 (100–143) ng·mL−1 versus Group 2 100 (100–2025) ng·mL−1#nsIndependent t-testsMedian (IQR)
    Sly [9]F (microbiology), P (aliquots 2 and 3)45 uninfectedInfants12 infectedInfantsGroup 1 31.3 (11.3–76.3) versus Group 2 169 (72.2–208.5)#Group 1 13.5 (8.3–26.1) versus Group 2 35.7 (25.3–44.7)¶Group 1 100 (100–100) ng·mL−1 versus Group 2 350 (100–1330) ng·mL−1+Group 1 260 (128–630) pg·mL−1 versus Group 2 770 (420–2120) pg·mL−1§Independent t-testsMedian (IQR)
    Armstrong [13]svBAL, P18 infected2.6±1.1 months10 noninfected, nonsymptomatic2.6±1.1 monthsGroup 1 153 (52–449) versus Group 2 15 (8–29)***Group 1 78 (52–94)% versus Group 2 0 (0–31)%***Group 1 1112 (582–2126) versus Group 2 24 (9–63)***Independent t-testMean (95% CI)
    Sly [9]F (microbiology), P (aliquots 2 and 3)24 no antistaphylococcal prophylaxis3.6 (3.4–4.8) months33
    antistaphylococcal prophylaxis
    3.6 (2.8–4.7) monthsnsnsnsnsIndependent t-tests
    Armstrong [26]F28 infectedInfants (age not reported)7 pristine
    17 uninfected
    Infants (age not reported)Group 1 11 (8.7–13) pg·mL−1 versus Group 2 pristine 2.2 (0.48–10) pg·mL−1 and uninfected 2.2 (1.8–2.6) pg·mL−1
    ***
    Wald testGeometric mean (95% CI)
    Armstrong [26]F50 infected13 pristineGroup 1 562 (407–777) versus Group 2 pristine 127 (76–210) and uninfected 106 (67–168)***Group 1 50 (39–65) versus Group 2 pristine 8.4 (5.2–14) and uninfected 7.1 (4.4–12)***Group 1 80 (66–90)% versus Group 2 pristine 0 (0–25)% and uninfected 20 (6–44)% of patients with free NE activity***Group 1 1153 (754–1762) pg·mL−1 versus Group 2 pristine 32 (15–72) pg·mL−1 and uninfected 49 (23–101) pg·mL−1***Wald testGeometric mean (95% CI)
    Rosenfeld [52]Not specified31 (≥105 CFU·mL−1)≤15 months at study entry29 (<105 CFU·mL−1)≤15 months at study entrynsnsGeneralised estimating equation
    Rosenfeld [52]Not specified31 (≥105 CFU·mL−1)≤15 months at study entry30 no pathogen≤15 months at study entryGroup 1 1145 (580–2264) versus Group 2 114 (63–206)***Group 1 1802 (1104–2942) versus Group 2 427 (269–679)ƒ¶Generalised estimating equationGeometric mean (95% CI)
    Rosenfeld [52]Not specifiedNot specified P. aeruginosa positive≤15 months at study entryNot specified other pathogen≤15 months at study entrynsGeneralised estimating equation
    Nixon [53]F20 symptomatic20.7±10.6 months34 asymptomatic15.7±9.7 monthsnsnsnsGeneralised estimating equation
    Nixon [53]F15 infected22.8±6.7 months39 uninfected15.9±10.9 monthsGroup 1 59 (47–70) versus Group 2 28 (21–35) ***nsGroup 1 641 (305–1350) versus Group 2 253 (158–406)##¶Generalised estimating equationMean and geometric mean (95% CI)
    Dakin [54]F8 infected23 months14 uninfected23 months90.8% >105 pathogens versus 24.1% <105 pathogens¶¶4600 pg·mL−1 >105 pathogens versus 1627 pg·mL−1 <105 pathogens++Independent t-test/ANOVA
    Brennan [30]F (microbiology), P (aliquots 2 and 3)9 infected1.55 (1.11–2.51) years15 uninfected1.58 (1.12–2.91) years667 (58–5342) infected versus 60 (39–91) noninfectedƒ52 (38–81)% infected versus 17.3 (9–29)% noninfected
    ***
    nsNot reportedMedian (IQR)
    Gutierrez [55]F6 (≥105 CFU·mL−1)35.3±21.3 months24 (<105 CFU·mL−1)22.1±13.3 months*** (right middle lobe)
    ns (lingula)
    §§ (right middle lobe)
    ¶¶ (lingula)
    Independent t-test
    Armstrong [39]F5 virus-infected6.5±5.3 months22 noninfected2.6±1.5 months169 (16, 1809) virus infected versus 16 (8, 34) noninfected***1372 (561, 3358) virus-infected versus 47 (21, 108) noninfected***ANCOVAGeometric mean (95% CI)
    Brennan [30]F (microbiology), P (aliquots 2 and 3)14 asymptomatic<6 years11 symptomatic<6 yearsGroup 1 60.3 (38.45–90.55) versus Group 2 667.58 (64.3–5341.48)ƒƒ,¶Group 1 16.5 (10.5–26.5) versus Group 2 53 (49.67–80.5)***nsNot reportedMedian (IQR)
    Sagel [56]P59 P. aeruginosa positive6 months–6 years31 no pathogens6 months–6 yearsGroup 1 5.6±0.7 log10·mL−1 versus Group 2 4.8±0.6 log10·mL−1***Group 1 49.3±25.9 versus Group 2 22.1±14.4***Group 1 41% of patients versus Group 2 0% of patients with NE detected in BAL***nsGroup 1 3.1±0.6 pg·mL−1 versus Group 2 2.3±0.6 pg·mL−1***Linear regressionMean±sd
    Sagel [56]P21 P. aeruginosa negative, other pathogen present6 months–6 years31 no pathogens6 months–6 yearsGroup 1 59±0.3 log10·mL−1 versus Group 2 5.6±0.3 log10·mL−1***Group 1 33.6±17.6 versus Group 2 22.1±14.4*nsnsGroup 1 2.8±0.7 pg·mL−1 versus Group 2 2.3±0.6 pg·mL−1**Linear regressionMean±sd
    Sagel [56]P59 P. aeruginosa positive6 months–6 years21 P. aeruginosa negative, other pathogen present6 months–6 yearsnsGroup 1 33.6±17.6 versus Group 2 22.1±14.4+nsnsnsLinear regressionMean±sd
    Sagel [57]P44 nonmucoid P. aeruginosa6 months–6 years15 mucoid P. aeruginosa6 months–6 yearsGroup 1 5.9±0.6 log10·mL−1 versus 5.5±0.7 log10·mL−1#Group 1 62.7±22.1 versus Group 2 44.5±25.7###nsnsnsLinear regressionMean±sd
    Sagel [56]PNot specified S. aureus present6 months–6 yearsNot specified S. aureus not present6 months–6 years***¶¶¶+***Linear regressionValues not reported
    Hilliard [45]P31 exacerbation6.2 years12 clinically well6.2 yearsGroup 1 1.0×106·mL−1 versus Group 2 0.4×106·mL−1*Nonparametric testsMedian
    Muhlebach [41]Not specifiedNot specified P. aeruginosa positiveMean 7.6 yearsNot specified other pathogenMean 1.9 yearsnsnsIndependent t-test
    Armstrong [15]Not specified14 infectedChildren (age not reported)20 noninfectedChildren (age not reported)Group 1 259 (70–968)×106·L−1 versus 17 (8–36)×106·L−1***Group 1 2013 (1164–3784) ng·L−1 versus Group 2 26 (13–51) ng·L−1***Independent t-testMean (95% CI)
    Noah [43]P15 infected<13 years10 uninfected<13 yearsGroup 1 3358 (100–11 520) versus Group 2 291 (25–952)*Group 1 84 (16–96) versus Group 2 40 (4–62)*nsnsKruskal–WallisMedian (range)
    Regamey [28]P36 during exacerbation10 stableGroup 1 970 (287–1584) versus Group 2 222 (21–380)¶¶¶Independent t-testMedian (IQR)
    Regamey [28]P13 Aspergillus present13 Aspergillus not presentnsIndependent t-test
    Regamey [28]P11 P. aeruginosa positive15 P. aeruginosa negativensIndependent t-test
    Bonfeld [33]P17 P. aeruginosa positiveAdolescents and adults (age not reported)5 P. aeruginosa negativeAdolescents and adults (age not reported)nsKruskal–Wallis
    Kirchner [40]P7 older patientsMean (range) 18.6 (13.5–31) years16 younger patientsMean (range) 10.5 (2–25) monthsnsKruskal–Wallis
    • Biomarkers are present at higher levels in patients with more severe lung disease. All samples are BAL, unless otherwise stated. PMN: polymorphonuclear; IL: interleukin; F: first; P: pooled; svBAL: small volume BAL; IQR: interquartile range; ns: not significant; P. aeruginosa: Pseudomonas aeruginosa; S. aureus: Staphylococcus aureus; NE: neutrophil elastase. *: p<0.05; **: p<0.01; ***: p<0.001; #: p=0.0001; ¶: p=0.027; +: p=0.003; §: p=0.036; ƒ: p=0.04; ##: p=0.03; ¶¶: p=0.01; ++: p=0.0001; §§: p=0.05; ƒƒ: p= 0.002; ###: p=0.02; ¶¶¶: p=0.004.

  • Table 4– Discriminate validity of bronchoalveolar lavage (BAL) inflammatory markers
    First author [ref.]Aliquot fraction analysedSubjectsAgeParticipantsResultsStatistics
    Khan [31]P160.08–0.97 yearsNeutrophil count
    PMN cell count above controls (n=11)
    PMN cell count overlapping controls (n=5)
    Lower SpO2 in group with elevated PMN cell count
    (mean±SEM 92.8±0.9 versus 96.6±0.7, p=0.0097) Weight-for-age ns
    Respiratory rate ns
    Wisconsin chest computed tomography score ns
    Independent t-test
    Sagel [57]P1116 months–6 yearsNeutrophil elastaseLower Shwachman scores in group with detectable free neutrophil elastase activity
    (63.5±8.8 versus 69.7±5.5, p<0.0001)
    Not reported
    Hull [58]F32Presence of inflammation (PMN cell count and IL-8)
    Inflammation (n=13)
    No inflammation (n=19)
    Higher lipid hydroperoxide concentration in group with detectable inflammation
    (geometric mean 97.7 versus 21.9 μM, p<0.05)
    Higher γ-GT in group with detectable inflammation
    (geometric mean 104.2 versus 20.2 U·L−1, p<0.05)
    Independent t-test
    • Data are presented as n, range or mean±sd, unless otherwise stated. Patients grouped by level of inflammation (from BAL biomarkers) differ in clinical presentation (including oxidative stress). P: pooled; F: first; PMN: polymorphonuclear; SpO2: arterial oxygen saturation measured by pulse oximetry; ns: nonsignificant; IL: interleukin; γ-GT: gamma glutamyl transpeptidase.

  • Table 5– Responsiveness of bronchoalveolar lavage (BAL) inflammatory markers
    First author [ref.]Aliquot fraction analysedSubjects nAgeInterventionResultsStatistical test Presentation of data
    PMN cell countsPMN cell %NEIL-6IL-8
    Response to treatment with antibiotics
     Armstrong [26]F1322.1 (14–44) monthsEradication of infection
    Follow-up BAL at 6–18 months
    Decreased
    T1 56.6%
    T2 21.2%
    Decreased
    T1 13.6 μg·mL−1
    T2 8.5 μg·mL−1
    Decreased
    T1 1782 pg·mL−1
    T2 307 pg·mL−1
    Mean
     Noah [18]Not specified1514–133 monthsTIS (inhaled 300 mg twice daily, 28 days) (n=6) versus ceftazidime and tobramycin (i.v., 14 days) (n=9)
    Follow-up BAL at 4–6 weeks
    p=0.02
    Inhaled +0.9 (0.6–5.4)
    Systemic -0.26 (0.03–2.26)
    ns
    Inhaled +5.4 (-11–15.3)
    Systemic -7.0 (-34.5–19.1)
    nsnsMann–Whitney U-test
    Median (range) ratio post versus pre
     Gibson [17]Not specified216 months–6 yearsTIS (inhaled, 28 days) versus placebo
    Follow-up BAL at day 28
    nsnsnsNot reported
     Gibson [16]Not specified96 months–6 yearsTIS (28 days)
    Follow-up BAL at day 56
    nsnsnsnsOne-sample t-test
     Gibson [16]Not specified96 months–6 yearsTIS (28 days)
    Follow-up BAL at day 84
    nsp=0.01
    T1 60.5 (29.4)
    T2 38.8 (18.2)
    nsnsOne-sample t-test
     Gibson [16]Not specified126 months–6 yearsTIS (56 days)
    Follow-up BAL at day 112
    nsp=0.01
    T1 53.4 (13.5)
    T2 35.4 (20.3)
    nsnsOne-sample t-test
     Gibson [16]Not specified86 months–6 yearsTIS (28 days)
    Follow-up BAL at day 112
    nsnsnsnsOne-sample t-test
     Meyer [61]P1117–40 yearsi.v. antibiotics for respiratory exacerbation
    BAL start and end of 2 weeks admission
    nsp=0.017Not reported
    Acquisition of infection
     Armstrong [26]F820 (13–50) monthsNo infection in first BAL (T1) but present in second
    Follow-up BAL at 6–18 months (T2)
    Increased
    T1 9.7%
    T2 55%
    Increased
    T1 3.3 μg·mL−1
    T2 10.3 μg·mL−1
    Increased
    T1 88 pg·mL−1
    T2 1206 pg·mL−1
    Mean
     Armstrong [13]F927±12 monthsNo infection in first BAL, but present in second
    Follow-up BAL at 6–18 months
    nsp<0.05
    Fold change 2.0 (95% CI 1.2–3.2)
    p<0.05
    Fold change 2.3 (95% CI -1.06–5.2)
    ANCOVA
    DNase
     Ratjen [21]F, P (2 and 3)29
    Treated group
    5–25 yearsTreated group (DNase inhaled 2.5 mg once daily, 18 months) versus untreated group (no DNase)
    Follow-up BAL at 18 months
    nsUnpaired t-test
    19
    Untreated group
    5–25 years
     Paul [19]F, P (2 and 3)46
    Treated group
    11.3±5.1 yearsTreated group (DNase inhaled, 36 months) versus untreated group (no DNase)
    Follow-up BAL at 18 and 36 months
    Increase more pronounced in untreated group (p<0.005) than the treated group (p<0.01)Increased in untreated group (p<0.007) but remained stable in treated groupIncreased in untreated group (p<0.02) but remained stable in treated groupNonparametric repeated measures analyses of variance
    39
    Untreated group
    12.2±4.4 years
     Ratjen [20]F, P (2 and 3)13
    Treated group
    6–18 yearsTreated group (DNase inhaled 2.5 mg once daily, 18 months) versus untreated group (no DNase)
    Follow-up BAL at 18 months
    Decreased in treated group
    -15 (-40–58)
    Increased in untreated group
    20 (-49–48)
    ns between groups
    Median (range)
    Mann–Whitney U-test
    10
    Untreated group
    6–18 years
    rSLPI
     McGarvey [6]P1627±2 yearsrSLPI (nebuliser 100 mg, twice daily, 1 week)
    Follow-up BAL 12 after the last aerosol
    p<0.03
    Average decrease 68%
    Not reported
    • All samples are BAL unless stated. PMN: polymorphonuclear; NE: neutrophil elastase; IL: interleukin; F: first; NS: not specified; P: pooled; T1: first paired (range: 6–18 months) BAL sample; T2: second paired (range: 6–18 months) BAL sample; TIS: tobramycin inhalation solution; rSLPI: recombinant secretory leukocyte protease inhibitor.

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Vol 43 Issue 2 Table of Contents
European Respiratory Journal: 43 (2)
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Clinimetric properties of bronchoalveolar lavage inflammatory markers in cystic fibrosis
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Clinimetric properties of bronchoalveolar lavage inflammatory markers in cystic fibrosis
Michael Fayon, Lisa Kent, Stephanie Bui, Lieven Dupont, Isabelle Sermet
European Respiratory Journal Feb 2014, 43 (2) 610-626; DOI: 10.1183/09031936.00017713

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Clinimetric properties of bronchoalveolar lavage inflammatory markers in cystic fibrosis
Michael Fayon, Lisa Kent, Stephanie Bui, Lieven Dupont, Isabelle Sermet
European Respiratory Journal Feb 2014, 43 (2) 610-626; DOI: 10.1183/09031936.00017713
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  • The pathophysiological role of novel pulmonary arterial hypertension gene SOX17
  • Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation
  • When things go wrong: Exploring possible mechanisms driving the progressive fibrosis phenotype in interstitial lung diseases
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