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.